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1.
J Am Soc Nephrol ; 33(8): 1487-1500, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35537780

RESUMO

BACKGROUND: The risk of cardiovascular events rises after AKI. Leukocytes promote atherosclerotic plaque growth and instability. We established a model of enhanced remote atherosclerosis after renal ischemia-reperfusion (IR) injury and investigated the underlying inflammatory mechanisms. METHODS: Atherosclerotic lesions and inflammation were investigated in native and bone marrow-transplanted LDL receptor-deficient (LDLr-/- ) mice after unilateral renal IR injury using histology, flow cytometry, and gene expression analysis. RESULTS: Aortic root atherosclerotic lesions were significantly larger after renal IR injury than in controls. A gene expression screen revealed enrichment for chemokines and their cognate receptors in aortas of IR-injured mice in early atherosclerosis, and of T cell-associated genes in advanced disease. Confocal microscopy revealed increased aortic macrophage proximity to T cells. Differential aortic inflammatory gene regulation in IR-injured mice largely paralleled the pattern in the injured kidney. Single-cell analysis identified renal cell types that produced soluble mediators upregulated in the atherosclerotic aorta. The analysis revealed a marked early increase in Ccl2, which CCR2+ myeloid cells mainly expressed. CCR2 mediated myeloid cell homing to the post-ischemic kidney in a cell-individual manner. Reconstitution with Ccr2-/- bone marrow dampened renal post-ischemic inflammation, reduced aortic Ccl2 and inflammatory macrophage marker CD11c, and abrogated excess aortic atherosclerotic plaque formation after renal IR. CONCLUSIONS: Our data introduce an experimental model of remote proatherogenic effects of renal IR and delineate myeloid CCR2 signaling as a mechanistic requirement. Monocytes should be considered as mobile mediators when addressing systemic vascular sequelae of kidney injury.


Assuntos
Injúria Renal Aguda , Aterosclerose , Placa Aterosclerótica , Traumatismo por Reperfusão , Camundongos , Animais , Aterosclerose/etiologia , Monócitos/metabolismo , Inflamação , Isquemia , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/metabolismo , Injúria Renal Aguda/etiologia , Camundongos Endogâmicos C57BL , Receptores CCR2 , Camundongos Knockout
2.
Int J Mol Sci ; 23(2)2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35054830

RESUMO

Chronic kidney disease (CKD) is characterized by a long-term loss of kidney function and, in most cases, by progressive fibrosis. Zinc-alpha2-glycoprotein (AZGP1) is a secreted protein, which is expressed in many different tissues and has been associated with a variety of functions. In a previous study, we have shown in cell culture and in AZGP1 deficient mice that AZGP1 has protective anti-fibrotic effects. In the present study, we tested the therapeutic potential of an experimental increase in AZGP1 using two different strategies. (1) C57Bl/6J mice were treated systemically with recombinant AZGP1, and (2) a transgenic mouse strain was generated to overexpress AZGP1 conditionally in proximal tubular cells. Mice underwent unilateral uretic obstruction as a pro-fibrotic kidney stress model, and kidneys were examined after 14 days. Recombinant AZGP1 treatment was accompanied by better preservation of tubular integrity, reduced collagen deposition, and lower expression of injury and fibrosis markers. Weaker but similar tendencies were observed in transgenic AZGP1 overexpressing mice. Higher AZGP1 levels led to a significant reduction in stress-induced accumulation of tubular lipid droplets, which was paralleled by improved expression of key players in lipid metabolism and fatty acid oxidation. Together these data show beneficial effects of elevated AZGP1 levels in fibrotic kidney disease and highlight a novel link to tubular cell lipid metabolism, which might open up new opportunities for CKD treatment.


Assuntos
Adipocinas/genética , Adipocinas/metabolismo , Túbulos Renais/citologia , Insuficiência Renal Crônica/terapia , Animais , Células Cultivadas , Colágeno/metabolismo , Modelos Animais de Doenças , Células HEK293 , Humanos , Túbulos Renais/metabolismo , Metabolismo dos Lipídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Cultura Primária de Células , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/metabolismo , Regulação para Cima
3.
Int J Mol Sci ; 23(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36362059

RESUMO

Cell-free hemoglobin (CFH), a pro-oxidant and cytotoxic compound that is released in hemolysis, has been associated with nephrotoxicity. Lung transplantation (LuTx) is a clinical condition with a high incidence of acute kidney injury (AKI). In this study, we investigated the plasma levels of CFH and haptoglobin, a CFH-binding serum protein, in prospectively enrolled LuTx patients (n = 20) with and without AKI. LuTx patients with postoperative AKI had higher CFH plasma levels at the end of surgery compared with no-AKI patients, and CFH correlated with serum creatinine at 48 h. Moreover, CFH levels inversely correlated with haptoglobin levels, which were significantly reduced at the end of surgery in LuTx patients with AKI. Because multiple other factors can contribute to AKI development in the complex clinical setting of LuTx, we next investigated the role of exogenous CFH administration in a mouse model of mild bilateral renal ischemia reperfusion injury (IRI). Exogenous administration of CFH after reperfusion caused overt AKI with creatinine increase, tubular injury, and enhanced markers of renal inflammation compared with vehicle-treated animals. In conclusion, CFH is a possible factor contributing to postoperative AKI after LuTx and promotes AKI in an experimental model of mild transient renal ischemia. Targeting CFH might be a therapeutic option to prevent AKI after LuTx.


Assuntos
Injúria Renal Aguda , Hemoglobinas , Transplante de Pulmão , Traumatismo por Reperfusão , Animais , Camundongos , Injúria Renal Aguda/diagnóstico , Creatinina/química , Haptoglobinas/metabolismo , Hemoglobinas/química , Hemoglobinas/metabolismo , Isquemia/metabolismo , Rim/metabolismo , Transplante de Pulmão/efeitos adversos , Reperfusão/efeitos adversos , Traumatismo por Reperfusão/metabolismo
4.
FASEB J ; 34(12): 16307-16318, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33089923

RESUMO

Postischemic acute kidney injury (AKI) is a common clinical complication and often fatal, with no effective treatment available. Little is known about the role of leukocytes trapped in renal vessels during ischemia-reperfusion injury (IRI) in the postischemic AKI. We designed a new animal model in rats with preforming renal artery lavage prior to IRI to investigate the effect of diminishing the residual circulating leukocytes on kidney damage and inflammation. Moreover, the functional changes of macrophages in hypoxia reoxygenation condition were also analyzed. We found pre-ischemic renal lavage significantly decreased the serum creatinine and blood urea nitrogen levels, and downregulated the mRNA and protein expressions in kidneys and urinary secretion of kidney injury molecule-1 of rats after IRI. The renal pathological damage caused by IRI was also ameliorated by pre-ischemic renal lavage, as evidenced by fewer cast formation, diminished morphological signs of AKI in the tissue at 24 hours after IRI. Pre-ischemic renal lavage reduced the numbers of infiltrating CD68+ macrophages and MPO+ neutrophils. The mRNA expression of pro-inflammatory mediator in IRI kidneys and the levels of pro-inflammatory cytokines in circulatory system and urine were also reduced due to pre-ischemic lavage. Compared with nontreated rats with IRI, pre-ischemic renal lavage significantly reduced the phosphorylation levels of ERK and p65 subunit of NF-κB in the kidney after IRI. In addition, we found hypoxia/reoxygenation could promote the expression of pro-inflammatory mediators and inhibit the expression of anti-inflammatory factors by regulating ERK/NF-κB signaling pathway. Thus, pre-ischemic renal lavage could clearly reduce the renal damage after IRI by attenuating inflammation, and macrophages trapped in renal vessels during IRI could be important pathogenic factors driving tissue injury.


Assuntos
Injúria Renal Aguda/patologia , Inflamação/patologia , Rim/patologia , Traumatismo por Reperfusão/patologia , Injúria Renal Aguda/metabolismo , Animais , Nitrogênio da Ureia Sanguínea , Linhagem Celular , Creatinina/metabolismo , Inflamação/metabolismo , Rim/metabolismo , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , NF-kappa B/metabolismo , Neutrófilos/metabolismo , Neutrófilos/patologia , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Artéria Renal/metabolismo , Artéria Renal/patologia , Traumatismo por Reperfusão/metabolismo , Transdução de Sinais/fisiologia
5.
J Am Soc Nephrol ; 31(5): 983-995, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32209589

RESUMO

BACKGROUND: Expression of SerpinB2, a regulator of inflammatory processes, has been described in the context of macrophage activation and cellular senescence. Given that mechanisms for these processes interact and can shape kidney disease, it seems plausible that SerpinB2 might play a role in renal aging, injury, and repair. METHODS: We subjected SerpinB2 knockout mice to ischemia-reperfusion injury or unilateral ureteral obstruction. We performed phagocyte depletion to study SerpinB2's role beyond the effects of macrophages and transplanted bone marrow from knockout mice to wild-type mice and vice versa to dissect cell type-dependent effects. Primary tubular cells and macrophages from SerpinB2 knockout and wild-type mice were used for functional studies and transcriptional profiling. RESULTS: Cultured senescent tubular cells, kidneys of aged mice, and renal stress models exhibited upregulation of SerpinB2 expression. Functionally, lack of SerpinB2 in aged knockout mice had no effect on the magnitude of senescence markers but associated with enhanced kidney damage and fibrosis. In stress models, inflammatory cell infiltration was initially lower in knockout mice but later increased, leading to an accumulation of significantly more macrophages. SerpinB2 knockout tubular cells showed significantly reduced expression of the chemokine CCL2. Macrophages from knockout mice exhibited reduced phagocytosis and enhanced migration. Macrophage depletion and bone marrow transplantation experiments validated the functional relevance of these cell type-specific functions of SerpinB2. CONCLUSIONS: SerpinB2 influences tubule-macrophage crosstalk by supporting tubular CCL2 expression and regulating macrophage phagocytosis and migration. In mice, SerpinB2 expression seems to be needed for coordination and timely resolution of inflammation, successful repair, and kidney homeostasis during aging. Implications of SerpinB2 in human kidney disease deserve further exploration.


Assuntos
Injúria Renal Aguda/enzimologia , Envelhecimento/imunologia , Senescência Celular/imunologia , Túbulos Renais/enzimologia , Rim/enzimologia , Macrófagos/fisiologia , Inibidor 2 de Ativador de Plasminogênio/fisiologia , Traumatismo por Reperfusão/enzimologia , Obstrução Ureteral/complicações , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/imunologia , Animais , Movimento Celular , Quimiocina CCL2/biossíntese , Quimiocina CCL2/genética , Técnicas de Cocultura , Indução Enzimática , Células Epiteliais/metabolismo , Fibrose , Homeostase , Rim/irrigação sanguínea , Rim/patologia , Masculino , Camundongos , Camundongos Knockout , Fagocitose , Inibidor 2 de Ativador de Plasminogênio/deficiência , Traumatismo por Reperfusão/imunologia , Transcriptoma , Obstrução Ureteral/enzimologia , Obstrução Ureteral/imunologia
6.
Am J Physiol Renal Physiol ; 319(4): F563-F570, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32799675

RESUMO

Acute kidney injury (AKI) frequently complicates major surgery and can be associated with hypertension and progress to chronic kidney disease, but reports on blood pressure normalization in AKI are conflicting. In the present study, we investigated the effects of an angiotensin-converting enzyme inhibitor, enalapril, and a soluble epoxide hydrolase inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), on renal inflammation, fibrosis, and glomerulosclerosis in a mouse model of ischemia-reperfusion injury (IRI)-induced AKI. Male CD1 mice underwent unilateral IRI for 35 min. Blood pressure was measured by tail cuff, and mesangial matrix expansion was quantified on methenamine silver-stained sections. Renal perfusion was assessed by functional MRI in vehicle- and TPPU-treated mice. Immunohistochemistry was performed to study the severity of AKI and inflammation. Leukocyte subsets were analyzed by flow cytometry, and proinflammatory cytokines were analyzed by quantitative PCR. Plasma and tissue levels of TPPU and lipid mediators were analyzed by liquid chromatography mass spectrometry. IRI resulted in a blood pressure increase of 20 mmHg in the vehicle-treated group. TPPU and enalapril normalized blood pressure and reduced mesangial matrix expansion. However, inflammation and progressive renal fibrosis were severe in all groups. TPPU further reduced renal perfusion on days 1 and 14. In conclusion, early antihypertensive treatment worsened renal outcome after AKI by further reducing renal perfusion despite reduced glomerulosclerosis.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Glomerulonefrite/prevenção & controle , Hipertensão/tratamento farmacológico , Compostos de Fenilureia/farmacologia , Piperidinas/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia , Injúria Renal Aguda/fisiopatologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Anti-Hipertensivos/toxicidade , Modelos Animais de Doenças , Progressão da Doença , Enalapril/farmacologia , Inibidores Enzimáticos/toxicidade , Epóxido Hidrolases/antagonistas & inibidores , Fibrose , Mesângio Glomerular/efeitos dos fármacos , Mesângio Glomerular/patologia , Mesângio Glomerular/fisiopatologia , Glomerulonefrite/etiologia , Glomerulonefrite/patologia , Glomerulonefrite/fisiopatologia , Hipertensão/etiologia , Hipertensão/fisiopatologia , Masculino , Camundongos , Compostos de Fenilureia/toxicidade , Piperidinas/toxicidade , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/fisiopatologia
7.
Kidney Int ; 97(1): 89-94, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31718844

RESUMO

Renal allograft rejection can be prevented by immunological tolerance, which may be associated with de novo formed lymphatic vessels in the donor kidney after transplantation in man. A suitable mouse model of renal allograft rejection in which lymphangiogenesis can be deliberately induced in the graft is critical for elucidating the mechanisms responsible for the association between attenuated transplant rejection and abundance of lymphatic vessels. Here we describe the development of a novel mouse model of rapid renal transplant rejection in which transgenic induction of lymphangiogenesis in the immune-incompatible graft greatly extends its survival time. Thus, our novel approach may facilitate exploitation of lymphangiogenesis in the grafted organ.


Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Nefropatias/cirurgia , Transplante de Rim/efeitos adversos , Linfangiogênese/imunologia , Aloenxertos/imunologia , Aloenxertos/patologia , Animais , Modelos Animais de Doenças , Feminino , Técnicas de Introdução de Genes , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Humanos , Rim/imunologia , Rim/patologia , Longevidade/imunologia , Vasos Linfáticos/imunologia , Vasos Linfáticos/patologia , Masculino , Camundongos , Camundongos Transgênicos , Fator C de Crescimento do Endotélio Vascular/genética , Fator C de Crescimento do Endotélio Vascular/metabolismo
8.
Am J Physiol Renal Physiol ; 316(6): F1124-F1132, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30785352

RESUMO

Inhibition of p53 has been shown to be an efficient strategy for ameliorating kidney ischemia-reperfusion (I/R) injury in experimental models. The therapeutic value of p53 siRNA-based inhibition for I/R in renal transplantation is currently being evaluated in clinical studies. While the major rationale for these studies is the suppression of proapoptotic properties, there are more equally important injury response pathways regulated by p53. A p53-dependent pathway shown to be crucial for renal long-term outcome is cellular senescence. In this study, we tested the hypothesis that p53 siRNA reduces I/R-induced senescence and thereby improves kidney outcome. By comparing the impact of different treatment durations in a mouse model of renal I/R, we found that repetitive administration of p53 siRNA during the first 14 days after I/R reduced the senescence load and ameliorated the postischemic phenotype. Prolonged application of p53 siRNA over a 26-day period after I/R, however, did not provide any additional benefit for senescence reduction but reversed some of the renoprotective effects of the early treatment. These data suggest a time-dependent role of p53 activity supporting the current therapeutic concept of a short-term inhibition, while advocating against a prolonged treatment after I/R.


Assuntos
Injúria Renal Aguda/terapia , Senescência Celular , Túbulos Renais Proximais/metabolismo , RNA Interferente Pequeno/administração & dosagem , Terapêutica com RNAi , Traumatismo por Reperfusão/terapia , Proteína Supressora de Tumor p53/metabolismo , Injúria Renal Aguda/genética , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Apoptose , Modelos Animais de Doenças , Túbulos Renais Proximais/patologia , Masculino , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/toxicidade , Terapêutica com RNAi/efeitos adversos , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Fatores de Tempo , Proteína Supressora de Tumor p53/genética
9.
Kidney Int ; 95(6): 1405-1417, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30948201

RESUMO

Peritoneal dialysis (PD) is limited by chronic fibrotic remodeling of the peritoneal wall, a transforming growth factor-ß (TGF-ß)-mediated process. The fractalkine (CX3CL1) receptor CX3CR1 is expressed on macrophages and monocytes, where it is a marker of TGFß expression. Detection of its ligand CX3CL1 on the peritoneal mesothelium led us to hypothesize a pathophysiologic role of CX3CL1-CX3CR1 interaction in peritoneal fibrosis. We found that CX3CL1 was expressed on peritoneal mesothelial cells from PD patients and in a murine PD model. CX3CR1, mostly expressed on macrophages in the peritoneal wall, promoted fibrosis induced by chronic dialysate exposure in the mouse model. Our data suggest a positive feedback loop whereby direct interaction with CX3CR1-expressing macrophages promotes mesothelial expression of CX3CL1 and TGFß expression. In turn, TGFß upregulates CX3CR1 in murine and human monocytic cells. Upstream, macrophage cytokines including interleukin-1ß (IL-1ß) promote mesothelial CX3CR1 and TGFß expression, providing a starting point for CX3CL1-CX3CR1 interaction. IL-1ß expression was enhanced by exposure to dialysate both in vitro and in the mouse models. Our data suggest that macrophage-mesothelial cell crosstalk through CX3CR1-CX3CL1 interaction enhances mesothelial TGFß production, promoting peritoneal fibrosis in response to dialysate exposure. This interaction could be a novel therapeutic target in PD-associated chronic peritoneal fibrosis.


Assuntos
Receptor 1 de Quimiocina CX3C/metabolismo , Quimiocina CX3CL1/metabolismo , Fibrose Peritoneal/patologia , Idoso , Animais , Comunicação Celular , Linhagem Celular , Células Cultivadas , Técnicas de Cocultura , Soluções para Diálise/toxicidade , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Feminino , Humanos , Interleucina-1beta/metabolismo , Leucócitos Mononucleares , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Diálise Peritoneal/efeitos adversos , Fibrose Peritoneal/etiologia , Peritônio/citologia , Peritônio/patologia , Cultura Primária de Células , Insuficiência Renal Crônica/terapia , Fator de Crescimento Transformador beta/metabolismo , Regulação para Cima
10.
Nephrol Dial Transplant ; 34(6): 947-960, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30247663

RESUMO

BACKGROUND: Peritoneal membrane (PM) damage during peritoneal dialysis (PD) is mediated largely by high glucose (HG)-induced pro-inflammatory and neo-angiogenic processes, resulting in PM fibrosis and ultrafiltration failure. We recently demonstrated a crucial role for protein kinase C (PKC) isoform α in mesothelial cells. METHODS: In this study we investigate the role of PKCß in PM damage in vitro using primary mouse peritoneal macrophages (MPMΦ), human macrophages (HMΦ) and immortalized mouse peritoneal mesothelial cells (MPMCs), as well as in vivo using a chronic PD mouse model. RESULTS: We demonstrate that PKCß is the predominant classical PKC isoform expressed in primary MPMΦ and its expression is up-regulated in vitro under HG conditions. After in vitro lipopolysaccharides stimulation PKCß-/- MPMΦ demonstrates increased levels of interleukin 6 (IL-6), tumour necrosis factor α, and monocyte chemoattractant protein-1 and drastically decrease IL-10 release compared with wild-type (WT) cells. In vivo, catheter-delivered treatment with HG PD fluid for 5 weeks induces PKCß up-regulation in omentum of WT mice and results in inflammatory response and PM damage characterized by fibrosis and neo-angiogenesis. In comparison to WT mice, all pathological changes are strongly aggravated in PKCß-/- animals. Underlying molecular mechanisms involve a pro-inflammatory M1 polarization shift of MPMΦ and up-regulation of PKCα in MPMCs of PKCß-/- mice. Finally, we demonstrate PKCß involvement in HG-induced polarization processes in HMΦ. CONCLUSIONS: PKCß as the dominant PKC isoform in MPMΦ is up-regulated by HG PD fluid and exerts anti-inflammatory effects during PD through regulation of MPMΦ M1/M2 polarization and control of the dominant mesothelial PKC isoform α.


Assuntos
Macrófagos/metabolismo , Diálise Peritoneal/efeitos adversos , Proteína Quinase C beta/deficiência , Animais , Quimiocina CCL2/metabolismo , Soluções para Diálise/metabolismo , Modelos Animais de Doenças , Células Epiteliais , Epitélio , Feminino , Glucose/metabolismo , Humanos , Inflamação , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Transgênicos , Neovascularização Patológica , Omento/metabolismo , Fibrose Peritoneal/metabolismo , Peritônio/metabolismo , Isoformas de Proteínas , Proteína Quinase C-alfa/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima
11.
J Clin Nurs ; 28(17-18): 3299-3309, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31066115

RESUMO

AIMS AND OBJECTIVES: To evaluate the effectiveness of a self-efficacy-focused structured education programme on outcomes in adults with type 2 diabetes (T2DM) without insulin therapy. BACKGROUND: Structured education regarding metabolic control in T2DM adults without insulin therapy has not always been effective, and this lack of effectiveness might be due to overlooking self-efficacy. Whether a self-efficacy-focused structured education programme could improve metabolic and psychosocial outcomes for T2DM adults more effectively remains unknown. DESIGN: A multicentre parallel randomised controlled concealed label trial. METHODS: The study conducted in outpatients of four hospitals in China. A total of 265 T2DM adults without insulin therapy were randomly assigned to an intervention group of a self-efficacy-focused structured education programme (n = 133), or to a control group of routine education (n = 132). The differences in metabolic and psychosocial outcomes were investigated at baseline, three- and 6-month follow-ups. RESULTS: The primary outcome of A1C and the secondary outcomes of weight, body mass index, waist circumference, diastolic pressure, self-efficacy, self-management behaviours and knowledge improved significantly in the intervention group compared with the control group at 6-month follow-up. The differences in A1C between groups for patients with a low educational background at 6-month follow-up were significant. No significant differences were found in other secondary outcomes of systolic pressure, the blood lipid profile and diabetes distress between groups at 6-month follow-up. CONCLUSIONS: This programme can improve glycaemic control, weight control, diastolic pressure, self-efficacy, self-management behaviours and diabetes knowledge for T2DM adults. RELEVANCE TO CLINICAL PRACTICE: This self-efficacy-focused structured education programme is effective and can be incorporated into regular clinical care and led by trained staff (e.g. nurses), and it can be implemented in patients with low educational backgrounds.


Assuntos
Diabetes Mellitus Tipo 2/dietoterapia , Autoeficácia , Adulto , China , Diabetes Mellitus Tipo 2/psicologia , Feminino , Educação em Saúde/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Desenvolvimento de Programas
12.
Int J Mol Sci ; 20(10)2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31137652

RESUMO

The presence of B-cell clusters in allogenic T cell-mediated rejection (TCMR) of kidney allografts is linked to more severe disease entities. In this study we characterized B-cell infiltrates in patients with TCMR and examined the role of serum CXCL-13 in these patients and experimentally. CXCL-13 serum levels were analyzed in 73 kidney allograft recipients at the time of allograft biopsy. In addition, four patients were evaluated for CXCL13 levels during the first week after transplantation. ELISA was done to measure CXCL-13 serum levels. For further mechanistic understanding, a translational allogenic kidney transplant (ktx) mouse model for TCMR was studied in BalbC recipients of fully mismatched transplants with C57BL/6 donor kidneys. CXCL-13 serum levels were measured longitudinally, CD20 and CD3 composition and CXCL13 mRNA in tissue were examined by flow cytometry and kidneys were examined by histology and immunohistochemistry. We found significantly higher serum levels of the B-cell chemoattractant CXCL13 in patients with TCMR compared to controls and patients with borderline TCMR. Moreover, in patients with acute rejection within the first week after ktx, a >5-fold CXCL13 increase was measured and correlated with B-cell infiltrates in the biopsies. In line with the clinical findings, TCMR in mice correlated with increased systemic serum-CXCL13 levels. Moreover, renal allografts had significantly higher CXCL13 mRNA expression than isogenic controls and showed interstitial CD20+ B-cell clusters and CD3+ cell infiltrates accumulating in the vicinity of renal vessels. CXCL13 blood levels correlate with B-cell involvement in TCMR and might help to identify patients at risk of a more severe clinical course of rejection.


Assuntos
Quimiocina CXCL13/sangue , Rejeição de Enxerto/sangue , Transplante de Rim/efeitos adversos , Adulto , Animais , Linfócitos B/imunologia , Biomarcadores/sangue , Rejeição de Enxerto/imunologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Linfócitos T/imunologia
13.
Am J Physiol Renal Physiol ; 314(5): F881-F892, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29357437

RESUMO

Renal ischemia-reperfusion injury (IRI) is a severe complication of major surgery and a risk factor for increased morbidity and mortality. Here, we investigated mechanisms that might contribute to IRI-induced progression to chronic kidney disease (CKD). Acute kidney injury (AKI) was induced by unilateral IRI for 35 min in CD1 and C57BL/6 (B6) mice. Unilateral IRI was used to overcome early mortality. Renal morphology, NGAL upregulation, and neutrophil infiltration as well as peritubular capillary density were studied by immunohistochemistry. The composition of leukocyte infiltrates in the kidney after IRI was investigated by flow cytometry. Systemic blood pressure was measured with a tail cuff, and renal perfusion was quantified by functional magnetic resonance imaging (fMRI). Mesangial matrix expansion was assessed by silver staining. Following IRI, CD1 and B6 mice developed similar morphological signs of AKI and increases in NGAL expression, but neutrophil infiltration was greater in CD1 than B6 mice. IRI induced an increase in systemic blood pressure of 20 mmHg in CD1, but not in B6 mice; and CD1 mice also had a greater loss of renal perfusion and kidney volume than B6 mice ( P < 0.05). CD1 mice developed substantial interstitial fibrosis and decreased peritubular capillary (PTC) density by day 14 while B6 mice showed only mild renal scarring and almost normal PTC. Our results show that after IRI, CD1 mice develop more inflammation, hypertension, and later mesangial matrix expansion than B6 mice do. Subsequently, CD1 animals suffer from CKD due to impaired renal perfusion and pronounced permanent loss of peritubular capillaries.


Assuntos
Injúria Renal Aguda/complicações , Hipertensão/etiologia , Rim/irrigação sanguínea , Circulação Renal , Insuficiência Renal Crônica/etiologia , Traumatismo por Reperfusão/complicações , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Injúria Renal Aguda/fisiopatologia , Animais , Velocidade do Fluxo Sanguíneo , Pressão Sanguínea , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Fibrose , Mesângio Glomerular/patologia , Hipertensão/metabolismo , Hipertensão/patologia , Hipertensão/fisiopatologia , Imuno-Histoquímica , Rim/metabolismo , Rim/patologia , Lipocalina-2/metabolismo , Imageamento por Ressonância Magnética , Masculino , Camundongos Endogâmicos C57BL , Infiltração de Neutrófilos , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/fisiopatologia , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Fatores de Tempo
14.
Kidney Int ; 94(4): 741-755, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29935951

RESUMO

Severe ischemia reperfusion injury (IRI) results in rapid complement activation, acute kidney injury and progressive renal fibrosis. Little is known about the roles of the C5aR1 and C5aR2 complement receptors in IRI. In this study C5aR1-/- and C5aR2-/- mice were compared to the wild type in a renal IRI model leading to renal fibrosis. C5a receptor expression, kidney morphology, inflammation, and fibrosis were measured in different mouse strains one, seven and 21 days after IRI. Renal perfusion was evaluated by functional magnetic resonance imaging. Protein abundance and phosphorylation were assessed with high content antibody microarrays and Western blotting. C5aR1 and C5aR2 were increased in damaged tubuli and even more in infiltrating leukocytes after IRI in kidneys of wild-type mice. C5aR1-/- and C5aR2-/- animals developed less IRI-induced inflammation and showed better renal perfusion than wild-type mice following IRI. C5aR2-/- mice, in particular, had enhanced tubular and capillary regeneration with less renal fibrosis. Anti-inflammatory IL-10 and the survival/growth kinase AKT levels were especially high in kidneys of C5aR2-/- mice following IRI. LPS caused bone marrow-derived macrophages from C5aR2-/- mice to release IL-10 and to express the stress response enzyme heme oxygenase-1. Thus, C5aR1 and C5aR2 have overlapping actions in which the kidneys of C5aR2-/- mice regenerate better than those in C5aR1-/- mice following IRI. This is mediated, at least in part, by differential production of IL-10, heme oxygenase-1 and AKT.


Assuntos
Heme Oxigenase-1/metabolismo , Interleucina-10/metabolismo , Túbulos Renais/patologia , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor da Anafilatoxina C5a/genética , Traumatismo por Reperfusão/genética , Animais , Proliferação de Células/genética , Células Cultivadas , Células Epiteliais , Fibrose , Inflamação/etiologia , Rim/diagnóstico por imagem , Túbulos Renais/metabolismo , Túbulos Renais/fisiopatologia , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Imageamento por Ressonância Magnética , Camundongos , Camundongos Knockout , Imagem de Perfusão , Fosforilação , Fatores de Proteção , Receptor da Anafilatoxina C5a/metabolismo , Regeneração/genética , Traumatismo por Reperfusão/complicações , Regulação para Cima
15.
J Magn Reson Imaging ; 48(6): 1586-1594, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29717788

RESUMO

BACKGROUND: Liver ischemia reperfusion injury (IRI) occurs during liver surgery or transplantation resulting in an inflammatory response, tissue damage, and functional impairment of the organ. PURPOSE: To assess the feasibility of T2 mapping for noninvasive quantification of liver edema after partial liver IRI in mice. STUDY TYPE: Prospective, experimental study. ANIMAL MODEL: Partial liver IRI was induced in C57BL/6-mice by transient clamping of the left lateral and median liver lobes for 35 (n = 8), 45 (n = 6), 60 (n = 17), or 90 minutes (n = 5). For comparison, healthy C57BL/6-mice were examined as controls (n = 9). FIELD STRENGTH/SEQUENCE: Functional liver MRI was performed on a 7T scanner using a respiratory-triggered multiecho spin-echo sequence. ASSESSMENT: Healthy control mice and mice with partial liver IRI on day 1 after surgery, and additionally on day 7 in a subgroup with 60 minutes IRI (n = 8) were examined. Maps of T2 relaxation time of liver tissue were used to assess distribution, severity of tissue edema (mean T2 time), and the percentage of edematous liver tissue. STATISTICAL TEST: One-way analysis of variance (ANOVA) with Tukey's honest significant difference (HSD), paired t-tests, Pearson's test for correlation of MRI parameters with levels of liver enzymes, and histopathology, receiver operating characteristic (ROC) analysis. RESULTS: Significant tissue edema induced by liver IRI as compared to the control group was detected by increased mean T2 times in groups with 60 minutes (P < 0.001) and 90 minutes IRI (P < 0.001). The percentage of edematous liver tissue significantly increased with longer ischemia times (controls 3.4 ± 0.4%, 35 minutes 5.3 ± 0.6%, 45 minutes 23.3 ± 7.6%, 60 minutes 39.7 ± 3.6%, 90 minutes 51.3 ± 4.5%). Mean T2 times and the percentage of edematous liver tissue significantly correlated with elevation of liver enzymes (P < 0.001), histological evidence of liver injury (r = 0.80 and r = 0.82, P < 0.001), and neutrophil infiltration (r = 0.70 and r = 0.74, P < 0.001). In the subgroup with follow-up, the severity (P < 0.01) and extent of liver edema decreased significantly over time (P < 0.01). DATA CONCLUSION: T2 mapping allows quantification and follow-up of liver injury in mice. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1586-1594.


Assuntos
Edema/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Fígado/diagnóstico por imagem , Fígado/patologia , Traumatismo por Reperfusão/diagnóstico por imagem , Algoritmos , Animais , Meios de Contraste , Modelos Animais de Doenças , Inflamação , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos
16.
Eur Radiol ; 28(10): 4455-4464, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29713782

RESUMO

OBJECTIVE: To evaluate Gd-EOB-DTPA-enhanced MRI for quantitative assessment of liver organ damage after hepatic ischaemia reperfusion injury (IRI) in mice. METHODS: Partial hepatic IRI was induced in C57Bl/6 mice (n = 31) for 35, 45, 60 and 90 min. Gd-EOB-DTPA-enhanced MRI was performed 1 day after surgery using a 3D-FLASH sequence. A subgroup of n = 9 animals with 60 min IRI underwent follow-up with MRI and histology 7 days after IRI. The total liver volume was determined by manual segmentation of the entire liver. The volume of functional, contrast-enhanced liver parenchyma was quantified by a region growing algorithm (visual threshold) and an automated segmentation (Otsu's method). The percentages of functional, contrast-enhanced and damaged non-enhanced parenchyma were calculated according to these volumes. MRI data was correlated with serum liver enzyme concentrations and histologically quantified organ damage using periodic acid-Schiff (PAS) staining. RESULTS: The percentage of functional (contrasted) liver parenchyma decreased significantly with increasing ischaemia times (control, 94.4 ± 3.3%; 35 min IRI, 89.3 ± 4.1%; 45 min IRI, 87.9 ± 3.3%; 60 min IRI, 68 ± 10.5%, p < 0.001 vs. control; 90 min IRI, 55.9 ± 11.5%, p < 0.001 vs. control). The percentage of non-contrasted liver parenchyma correlated with histologically quantified liver organ damage (r = 0.637, p < 0.01) and serum liver enzyme elevations (AST r = 0.577, p < 0.01; ALT r = 0.536, p < 0.05). Follow-up MRI visualized recovery of functional liver parenchyma (71.5 ± 8.7% vs. 84 ± 2.1%, p < 0.05), consistent with less histological organ damage on day 7. CONCLUSION: We demonstrated the feasibility of Gd-EOB-DTPA-enhanced MRI for non-invasive quantification of damaged liver parenchyma following IRI in mice. This novel methodology may refine the characterization of liver disease and could have application in future studies targeting liver organ damage. KEY POINTS: • Prolonged ischaemia times in partial liver IRI increase liver organ damage. • Gd-EOB-DTPA-enhanced MRI at hepatobiliary phase identifies damaged liver volume after hepatic IRI. • Damaged liver parenchyma quantified with MRI correlates with histological liver damage. • Hepatobiliary phase Gd-EOB-DTPA-enhanced MRI enables non-invasive assessment of recovery from liver injury.


Assuntos
Meios de Contraste , Gadolínio DTPA , Hepatopatias/diagnóstico por imagem , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Traumatismo por Reperfusão/complicações , Animais , Biomarcadores/sangue , Técnicas Histológicas , Fígado/patologia , Hepatopatias/etiologia , Hepatopatias/patologia , Masculino , Camundongos Endogâmicos C57BL
17.
Am J Physiol Renal Physiol ; 313(2): F326-F338, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28515172

RESUMO

Kidney transplantation (KTX) is a life-saving procedure for patients with end-stage renal disease. Expression levels of many genes in the kidney vary between males and females, which may play an essential role in the sex differences in graft function. However, whether these differences are affected after cross-sex-KTX is unknown. In the present study, we assessed postoperative changes in genotype, function, and inflammatory responses of the grafts in same-sex- and cross-sex-KTX. Single kidney transplants were performed between same and different sex C57BL/6 mice paired into four combination groups: female donor/female recipient (F/F); male donor/male recipient (M/M); female donor/male recipient (F/M); and male donor/female recipient (M/F). The remnant native kidney was removed 4 days posttransplant. Expression levels of genes related to the contractility of the afferent arteriole and tubular sodium reabsorption were assessed. Same-sex-KTX did not significantly alter the magnitude or sex difference pattern of gene expression in male or female grafts. Cross-sex-KTX showed an attenuated sex difference in gene expressions. The measurements of endothelin 1, endothelin ETA receptor, Na+-K--2Cl cotransporter 2 (NKCC2), and epithelial Na+ channels (ENaC) subunits exhibited decreases in M/F compared with M/M and increases in F/M compared with F/F. There were no significant differences in hemodynamics or sodium excretion in response to acute volume expansion for any sex combinations. Cross-sex-KTX stimulated more robust inflammatory responses than same-sex-KTX. IL-6 and KC mRNA levels elevated 5- to 20-fold in cross-sex-KTX compared with same-sex-KTX. In conclusion, cross-sex-KTX alters gene expression levels and induces inflammatory responses, which might play an important role in long-term graft function.


Assuntos
Regulação da Expressão Gênica , Transplante de Rim/efeitos adversos , Rim/metabolismo , Rim/cirurgia , Nefrite/genética , Animais , Endotelina-1/genética , Endotelina-1/metabolismo , Canais Epiteliais de Sódio/genética , Canais Epiteliais de Sódio/metabolismo , Feminino , Interação Gene-Ambiente , Genótipo , Hemodinâmica , Mediadores da Inflamação/metabolismo , Rim/irrigação sanguínea , Rim/patologia , Masculino , Camundongos Endogâmicos C57BL , Modelos Animais , Nefrite/metabolismo , Nefrite/patologia , Nefrite/fisiopatologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Angiotensina/genética , Receptores de Angiotensina/metabolismo , Receptores de Endotelina/genética , Receptores de Endotelina/metabolismo , Circulação Renal , Eliminação Renal , Fatores Sexuais , Sódio/metabolismo , Trocador 3 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/genética , Trocadores de Sódio-Hidrogênio/metabolismo , Membro 1 da Família 12 de Carreador de Soluto/genética , Membro 1 da Família 12 de Carreador de Soluto/metabolismo , Membro 3 da Família 12 de Carreador de Soluto/genética , Membro 3 da Família 12 de Carreador de Soluto/metabolismo , Fatores de Tempo
18.
Kidney Int ; 92(3): 646-656, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28396121

RESUMO

Chronic renal allograft dysfunction (CAD) is a major limiting factor of long-term graft survival. It is characterized by interstitial fibrosis and tubular atrophy. The underlying pathomechanisms are incompletely understood. MicroRNAs are powerful regulators of gene expression and may have an impact on various diseases by direct mRNA decay or translational inhibition. A murine model of allogenic kidney transplantation was used resulting in CAD at 6 weeks after kidney transplantation. We identified fibrosis-associated miR-21a-5p by whole miRNAome expression analysis to be among the most highly upregulated miRNAs. In vitro in renal fibroblasts, miR-21a-5p was transcriptionally activated by interleukin 6-induced signal transducer and activator of transcription 3. Co-culture of LPS-activated macrophages with renal fibroblasts increased expression levels of miR-21a-5p and markers of fibrosis and inflammation. In addition, mature miR-21a-5p was secreted by macrophages in small vesicles, which were internalized by renal fibroblasts, thereby promoting profibrotic and proinflammatory effects. Notch2 receptor was identified as a potential target of miR-21a-5p and validated by luciferase gene reporter assays. Therapeutic silencing of miR-21a-5p in mice after allogenic kidney transplantation resulted in an amelioration of CAD, as indicated by a reduction in fibrosis development, inflammatory cell influx, tissue injury and BANFF lesion scoring. In a life-supporting model, miR-21a-5p antagonism had beneficial effects on kidney function. miR-21a-5p silencing may therefore be a viable therapeutic option in the treatment of patients following kidney transplantation to halt the development of CAD.


Assuntos
Aloenxertos/patologia , Rejeição de Enxerto/genética , Transplante de Rim/efeitos adversos , Rim/patologia , MicroRNAs/metabolismo , Receptor Notch2/genética , Animais , Biomarcadores/metabolismo , Doença Crônica , Técnicas de Cocultura , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Fibroblastos , Fibrose , Perfilação da Expressão Gênica , Sobrevivência de Enxerto/genética , Humanos , Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Oligonucleotídeos/genética , Receptor Notch2/metabolismo , Transplante Homólogo/efeitos adversos , Regulação para Cima
19.
J Magn Reson Imaging ; 46(6): 1664-1672, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28342287

RESUMO

PURPOSE: To examine the longitudinal changes of renal perfusion due to acute and chronic renal allograft rejection by using arterial spin labeling (ASL) MRI in translational mouse models of isogenic and allogenic kidney transplantation (ktx). MATERIALS AND METHODS: Acute rejection was induced by allogenic ktx of C57BL/6 (B6)-kidney grafts to BALB/c-recipients with prolonged cold ischemia (CIT) of 60 minutes (n = 13). To induce chronic rejection BALB/c-kidneys were transplanted into B6-recipients with short CIT of 30 minutes (n = 22). Isogenic grafts without rejection (n = 14 with prolonged, n = 9 with short CIT) and normal kidneys (n = 22) were used for comparison. Perfusion was measured on a 7T small-animal magnetic resonance imaging (MRI) scanner using flow-sensitive alternating inversion recovery (FAIR) ASL-sequences at day 1 and 6 (acute) or at week 3 and 6 (chronic) after surgery. Histological analyses of grafts included inflammation, vascular changes, and fibrosis. RESULTS: In the acute ktx model, ASL showed perfusion impairment in isogenic and allogenic kidney grafts. Perfusion of allografts further decreased until day 6 and remained stable in isografts without rejection (allogenic ktx 62 ± 21 vs. isogenic ktx 181 ± 39 ml/min/100g, P < 0.01). In the chronic ktx model, perfusion in isografts was similar to normal kidneys over the entire observation period. Perfusion was severely reduced in allografts compared to isografts (week 3: 28 ± 7 vs. 310 ± 46 ml/min/100g, P < 0.001, week 6: 32 ± 5 vs. 367 ± 72 ml/min/100g, P < 0.001). Histological analysis revealed severe inflammation, vascular occlusion, and rejection in allografts. Chronic rejection grafts showed endothelialitis, peritubular capillaritis, interstitial fibrosis, and tubular atrophy. CONCLUSION: ASL allows longitudinal assessment of renal perfusion impairment due to acute and chronic renal allograft rejection in translational mouse models. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1664-1672.


Assuntos
Rejeição de Enxerto/diagnóstico por imagem , Transplante de Rim , Rim/irrigação sanguínea , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Circulação Renal/fisiologia , Doença Aguda , Animais , Doença Crônica , Modelos Animais de Doenças , Rejeição de Enxerto/fisiopatologia , Rim/cirurgia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Marcadores de Spin
20.
J Am Soc Nephrol ; 27(6): 1753-64, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26449606

RESUMO

Reduced kidney function increases the risk for atherosclerosis and cardiovascular death. Leukocytes in the arterial wall contribute to atherosclerotic plaque formation. We investigated the role of fractalkine receptor CX3CR1 in atherosclerotic inflammation in renal impairment. Apoe(-/-) (apolipoprotein E) CX3CR1(-/-) mice with renal impairment were protected from increased aortic atherosclerotic lesion size and macrophage accumulation. Deficiency of CX3CR1 in bone marrow, only, attenuated atherosclerosis in renal impairment in an independent atherosclerosis model of LDL receptor-deficient (LDLr(-/-)) mice as well. Analysis of inflammatory leukocytes in atherosclerotic mixed bone-marrow chimeric mice (50% wild-type/50% CX3CR1(-/-) bone marrow into LDLr(-/-) mice) showed that CX3CR1 cell intrinsically promoted aortic T cell accumulation much more than CD11b(+)CD11c(+) myeloid cell accumulation and increased IL-17-producing T cell counts. In vitro, fewer TH17 cells were obtained from CX3CR1(-/-) splenocytes than from wild-type splenocytes after polarization with IL-6, IL-23, and TGFß Polarization of TH17 or TREG cells, or stimulation of splenocytes with TGFß alone, increased T cell CX3CR1 reporter gene expression. Furthermore, TGFß induced CX3CR1 mRNA expression in wild-type cells in a dose- and time-dependent manner. In atherosclerotic LDLr(-/-) mice, CX3CR1(+/-) T cells upregulated CX3CR1 and IL-17A production in renal impairment, whereas CX3CR1(-/-) T cells did not. Transfer of CX3CR1(+/-) but not Il17a(-/-) T cells into LDLr(-/-)CX3CR1(-/-) mice increased aortic lesion size and aortic CD11b(+)CD11c(+) myeloid cell accumulation in renal impairment. In summary, T cell CX3CR1 expression can be induced by TGFß and is instrumental in enhanced atherosclerosis in renal impairment.


Assuntos
Aterosclerose/etiologia , Inflamação/etiologia , Receptores de Quimiocinas/fisiologia , Insuficiência Renal/complicações , Animais , Receptor 1 de Quimiocina CX3C , Células Cultivadas , Feminino , Masculino , Camundongos , Receptores de Quimiocinas/genética
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