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1.
Biol Res ; 52(1): 50, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492196

RESUMO

BACKGROUND: Ureteral obstruction causes injury of the renal tissues and can irreversibly progress to renal fibrosis, with atrophy and apoptosis of tubular cells. The goal of the current study was to examine the effects of rhein on the apoptosis o renal tubular cells as well as renal fibrosis using a rodent model of unilateral ureteral obstruction (UUO). METHODS: UUO was induced through ureteral ligation, then animals received treatments with rhein or vehicle. The control rats only received sham operation. The renal tissue was harvested 1 week after surgery for assessment of kidney fibrosis. RESULTS: The expressions of collagen I and α-smooth muscle actin (α-SMA), as well as the severity of renal tubular apoptosis and fibrosis were time-dependently increased following UUO. Treatments with rhein partially inhibited such responses. Renal interstitial fibrosis was associated with STAT3 (signal transducer and activator of transcription 3) phosphorylation as well as altered expressions of Bax and Bcl2, both apoptosis-related proteins. Treatment with rhein also partly blocked these responses. CONCLUSION: These findings demonstrated that rhein mitigated apoptosis of renal tubular cell as well as renal fibrosis in a UUO rodent model. This curative effect is likely mediated via suppression of STAT3 phosphorylation.


Assuntos
Antraquinonas/administração & dosagem , Apoptose/efeitos dos fármacos , Rim/patologia , Obstrução Ureteral/prevenção & controle , Animais , Modelos Animais de Doenças , Progressão da Doença , Fibrose/metabolismo , Fibrose/patologia , Fibrose/prevenção & controle , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologia
2.
Rev Soc Bras Med Trop ; 52: e20180526, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31508780

RESUMO

INTRODUCTION: Crotalus envenomations cause serious complications and can be fatal without appropriate treatment. Venom isoforms present and inter/intraspecific variations in the venom composition can result in different symptoms presented by bites by snakes from the same species but from different geographical regions. We comparatively evaluated the local and systemic effects caused by Crotalus durissus terrificus (Cdt), C.d. collilineatus (Cdcolli), and C.d. cascavella (Cdcasc) envenomation. METHODS: Venom chromatography was performed. Proteolytic, phospholipase, and LAAO activities were analyzed. Edema, myotoxicity, hepatotoxicity, nephrotoxicity, and coagulation alterations were evaluated. RESULTS: The venom SDS-PAGE analyses found the presence of convulxin, gyroxin, crotoxin, and crotamine in Cdt and Cdcolli venoms. Crotamine was not present in the Cdcasc venom. Cdt, Cdcollli, and Cdcasc venoms had no proteolytic activity. Only Cdcasc and Cdt venoms had phospholipase activity. LAAO activity was observed in Cdcolli and Cdcasc venoms. Cdcolli and Cdcasc venoms caused 36.7% and 13.3% edema increases, respectively. Cdt venom caused a 10% edema induction compared to those by other venoms. All venoms increased TOTAL-CK, MB-CK, and LDH levels (indicating muscle injury) and ALT, AST, GGT, and ALP levels (markers of liver damage) and were able to induce a neuromuscular blockade. Urea and creatinine levels were also altered in both plasma and urine, indicating kidney damage. Only Cdcolli and Cdcasc venoms increased TAPP and TAP. CONCLUSIONS: Together, these results allow us to draw a distinction between local and systemic effects caused by Crotalus subspecies, highlighting the clinical and biochemical effects produced by their respective venoms.


Assuntos
Venenos de Crotalídeos/toxicidade , Crotalus/classificação , Edema/induzido quimicamente , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fosfatase Alcalina/sangue , Fosfatase Alcalina/efeitos dos fármacos , Animais , Creatina Quinase/sangue , Creatina Quinase/efeitos dos fármacos , Creatinina/sangue , Edema/patologia , Eletroforese em Gel de Poliacrilamida , Rim/patologia , L-Lactato Desidrogenase/sangue , L-Lactato Desidrogenase/efeitos dos fármacos , Fígado/patologia , Camundongos , Modelos Animais , Transaminases/sangue , Transaminases/efeitos dos fármacos , Ureia/sangue
4.
Zhonghua Yi Xue Za Zhi ; 99(35): 2756-2760, 2019 Sep 17.
Artigo em Chinês | MEDLINE | ID: mdl-31550798

RESUMO

Objective: To analyze the diagnostic value of diffusion-weighted imaging (DWI) signal pattern in renal lesions with T(2)WI hypointensity. Methods: Retrospective analysis was performed on DWI imaging datasets of 135 renal lesions with hypointentsity on T(2)WI confirmed by surgery, biopsy, or follow-up in the First Medical Center of Chinese PLA General Hospital from February 2016 to February 2017.One hundred and thirty-five renal lesions,43 benign lesions(age from 28 to 70 years,mean age was 43.5 years, male 18 lesions and female 25 lesions) and 92 malignant lesions (age from 17 to 86 years, mean age was 54.1 years, male 62 lesions and female 30 lesions). DWI signal pattern was classified into six categories: homogeneously high signal, homogeneously low signal, heterogeneously high signal, high halo signal, high halo and nodular signal, and high nodular signal. The agreement between two observers were tested using kappa statistic. The statistical difference between DWI signal characteristics in benign and malignant lesions was analyzed with Chi-Square test. Diagnostic efficacy in differentiation of benign and malignant renal lesions using DWI signal pattern were calculated. Results: One hundred and thirty-five lesions were detected in 135 cases with T(2)WI hypointensity. There were 43 benign lesions and 92 malignant lesions. The agreement between two observers was very good (kappa value=0.878 6). In renal T(2)WI hypointensity lesions, the proportion of DWI homogeneous high signal, homogeneous low signal, heterogeneous high signal, high halo signal, high halo and nodular signal, high nodular signal was 4.7% (2/43), 25.6% (11/43), 30.2% (13/43), 18.6% (8/43), 11.6% (5/43), 9.3% (4/43), respectively. The proportion of malignant lesions was 10.9% (10/92), 0 (0/92), 17.4% (16/92), 13.0% (12/92), 56.5% (52/92) and 2.2% (2/92), respectively. The difference of high halo and nodules signal and homogeneous low signal was statistically significant (all P<0.01). The sensitivity, specificity, positive prediction value (PPV) and negative prediction value (NPV) of high halo and nodular signal for malignancy were 56.5% (52/92), 88.4%(38/43), 91.2% (52/57) and 48.7%(38/78), respectively and homogeneous low signal for benign lesions were 25.6% (11/43), 100.0% (92/92), 100.0% (11/11) and 74.2% (92/124), respectively. Conclusions: DWI signal features may facilitated the accurate diagnosis of renal lesions with T(2)WI hypointensity. Malignant lesions exhibit a higher propensity with high halo and nodular signal on DWI while benign lesions with homogeneous low signal.


Assuntos
Imagem de Difusão por Ressonância Magnética , Rim/diagnóstico por imagem , Rim/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Renais/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
5.
Medicine (Baltimore) ; 98(36): e17028, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490389

RESUMO

Vasculogenic mimicry (VM) involves a tubular structure with a basement membrane that is similar to and communicates with vessels but functions independent of blood vessels to nourish tumor cells, promote tumor progression, invasion, and metastasis, with reduced 5-year survival rates. Tumor cell proliferation, invasion, and metastasis are promoted by the epithelial-mesenchymal transition (EMT). Paired-related homeobox 1 (PRRX1), a newly discovered EMT inducer, has been shown to correlate with metastasis and prognosis in diverse cancer types. Cancerous inhibitor of protein phosphatase 2A (CIP2A) was initially recognized as an oncoprotein. In this study, we aimed to investigate the expression and clinical significance of the EMT markers PRRX1, CIP2A and VM in clear cell renal cell carcinoma (CCRCC) and their respective associations with clinicopathological parameters and survival.Expression of PRRX1, CIP2A and VM in whole CCRCC tissues from 110 patients was analyzed by immunohistochemical and histochemical staining. Fisher's exact test or the chi square test was used to assess associations with positive or negative staining of these markers and clinicopathological characteristics.Positive expression of CIP2A and VM presence was significantly higher and that of PRRX1 was significantly lower in CCRCC tissues than in corresponding normal tissues. Furthermore, positive expression of CIP2A and VM was significantly associated with tumor grade, size, lymph node metastasis (LNM) stage, and tumor node metastasis (TNM) stage and inversely associated with overall survival time (OST). Moreover, levels of PRRX1 were negatively associated with tumor grade, size, LNM stage, and TNM stage. The PRRX1 subgroup had a significantly longer OST time than did the PRRX1 subgroup. In multivariate analysis, high VM and CIP2A, tumor grade, LNM stage, TNM stage, and low PRRX1 levels were identified as potential independent prognostic factors for OST in CCRCC patients.VM and expression of CIP2A and PRRX1 represent promising biomarkers for metastasis and prognosis and potential therapeutic targets in CCRCC.


Assuntos
Autoantígenos/metabolismo , Carcinoma de Células Renais/metabolismo , Proteínas de Homeodomínio/metabolismo , Neoplasias Renais/metabolismo , Proteínas de Membrana/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Feminino , Humanos , Rim/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico
6.
Medicine (Baltimore) ; 98(36): e17049, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31490399

RESUMO

RATIONALE: Although chronic pyelonephritis and urolithiasis are established risk factors for squamous cell carcinoma (SCC), only a minority of patients with chronic urolithiasis eventually develop SCC. It is believed that the chronic irritation leads to squamous cell metaplasia that may subsequently develop into SCC. Although studies show that SSC generally spreads locally with associated symptoms of lymphadenopathy, metastasis to the lungs and liver have also been reported. However, cases spreading to the flank have yet to be reported. Therefore, the use of reconstructive techniques for the repair of extensive soft tissue defects in the flank region after extended retroperitoneal resection, is unknown. PATIENT CONCERNS: We report a 54-year-old man who presented with a 1-month history of an enlarged skin mass on the right flank. DIAGNOSES: The patient was subsequently diagnosed with metastatic SCC involving the patient's integumentary system near the flank region proximal to the right kidney following percutaneous nephrostomy. INTERVENTIONS: The skin mass and the surrounding muscle tissue of the right flank were excised with a wide resection margin including radial nephrectomy. The soft tissue defect after resection was reconstructed using a unilateral gluteus maximus myocutaneous V-Y advancement flap. OUTCOMES: No recurrence of the SSC was found on follow-up CT performed 12 months postoperatively. LESSONS: In patients with long-standing nephrolithiasis complicated by staghorn stone-related infections, biopsies from suspicious lesions detected during percutaneous nephrolithotomy may facilitate early diagnosis. The modified gluteus maximus V-Y advancement flap may be a useful technique for the reconstruction of extensive soft-tissue defects involving the flank region.


Assuntos
Carcinoma de Células Escamosas/secundário , Neoplasias Renais/patologia , Rim/patologia , Neoplasias Cutâneas/secundário , Cálculos Coraliformes/complicações , Carcinoma de Células Escamosas/cirurgia , Humanos , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Nefrectomia , Neoplasias Cutâneas/cirurgia , Cálculos Coraliformes/diagnóstico por imagem , Retalhos Cirúrgicos
7.
Acta Cir Bras ; 34(7): e201900706, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31531540

RESUMO

PURPOSE: To investigate the protective roles of pyracantha fortune fruit extract (PFE) on acute renal toxicity induced by cadmium chloride (CdCl2) in rats. METHODS: Rats were pretreated with PFE and consecutively injected with CdCl2 (6.5 mg/kg) for 5 days. RESULTS: The concentration of Cd, kidney weight, malondialdehyde (MDA), and nitric oxide (NO) production were remarkably increased in CdCl2 group as well as the levels of plasma uric acid, urea, and creatinine (P < 0.001). However, the body weight and glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione peroxidase (GR) levels were markedly reduced by CdCl2 treatment (P < 0.001). Histological manifestations of renal tissue showed severely adverse changes. Moreover, CdCl2 treatment significantly decreased the B-cell lymphoma-2 (Bcl-2) expression while increased the Bcl-2-Associated X Protein (Bax), tumor necrosis factor-α (TNF-α) expression (P < 0.001). Additionally, the expression of Nrf2/Keap 1 related proteins Keap-1 gained a significant increase (P < 0.001), whereas the Nrf2, HO-1, γ-GCS, GSH-Px and NQO1 expression decreased by CdCl2 treatment (P < 0.05). These rats were pretreated with PFE to improve the changes caused by CdCl2 treatment. CONCLUSION: PFE could protect the kidney against acute renal toxicity induced by CdCl2.


Assuntos
Antioxidantes/farmacologia , Cloreto de Cádmio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Rim/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pyracantha/química , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Frutas/química , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Rim/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Superóxido Dismutase/metabolismo
9.
Methodist Debakey Cardiovasc J ; 15(2): 158-159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31384382

RESUMO

This column is supplied by Benjamin J. Lee, MD, MAS, an assistant professor of clinical medicine at both the Houston Methodist Institute for Academic Medicine and Weill Cornell Medical College. After earning his medical degree at Harvard Medical School, Dr. Lee completed a residency in internal medicine at the University of California, San Francisco (UCSF). He subsequently completed a nephrology fellowship at UCSF while simultaneously obtaining a Master of Advanced Study in clinical research from the UCSF Department of Epidemiology and Biostatistics. Dr. Lee is a Fellow of the American Society of Nephrology, a Certified Hypertension Specialist through the American Hypertension Specialist Certification Program, and a member of the American Society of Transplantation. He maintains his clinical practice with the Houston Kidney Consultants.


Assuntos
Cianose/etiologia , Cardiopatias Congênitas/complicações , Nefropatias/etiologia , Rim/fisiopatologia , Cianose/diagnóstico , Cianose/fisiopatologia , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/tratamento farmacológico , Cardiopatias Congênitas/fisiopatologia , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Nefropatias/diagnóstico , Nefropatias/tratamento farmacológico , Nefropatias/fisiopatologia , Prognóstico , Fatores de Risco
10.
Medicine (Baltimore) ; 98(33): e16641, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31415358

RESUMO

RATIONALE: Hybrid oncocytic/chromophobe tumor (HOCT) is defined as tumor composed of renal oncocytoma (RO) and chromophobe renal cell carcinoma (CHRCC). Sporadic HOCT is extremely rare, the preoperative diagnosis is difficult, and no guidelines for clinical therapy. We report a case who is the youngest male patient of sporadic HOCT in the world, review the previously reported cases, and share the clinical features, diagnosis, treatment, and prognosis of HOCT. PATIENT CONCERNS: A 30-year-old man was admitted with the complaints of incidental right renal tumor detected by abdominal ultrasound. He had no complaints of urological symptoms, abdominal pain, osphyalgia, and hematuria. Abdominal contrast-enhanced computed tomography revealed an 85 mm × 80 mm × 80 mm unilateral and solid renal mass, and no findings of metastases. DIAGNOSIS: The preoperative diagnosis was right renal tumor. INTERVENTIONS: Laparoscopic right radical nephrectomy was performed. OUTCOMES: Histopathology demonstrated a mixture of cells with the morphologic features of those seen in CHRCC and RO. The patient was final diagnosed as sporadic HOCT. After follow-up of 14 months, the patient had no complaints and evidence of disease recurrence. LESSONS: Sporadic HOCT is extremely rare. It is possible that core biopsy could improve diagnostic accuracy. Laparoscopic radical nephrectomy or nephron sparing surgery should be considered the clinical therapy of the sporadic HOCT patients. The clinical behavior of HOCT is still entirely uncertain and should be proved by studies with available long follow-up.


Assuntos
Adenoma Oxífilo/patologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Adenoma Oxífilo/cirurgia , Adulto , Carcinoma de Células Renais/cirurgia , Humanos , Rim/patologia , Neoplasias Renais/cirurgia , Masculino , Nefrectomia/métodos , Células Oxífilas/patologia
11.
Sud Med Ekspert ; 62(4): 58-60, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31407708

RESUMO

Eating mushrooms known to contain amatoxin is fraught with serious complications. The analysis of the relevant literature publications revealed no article with the description of the histological picture of the internal organs in the subjects intoxicated with amatoxin. It is known, however, that such poisoning is associated with the severe irreversible injuries to all intracellular protein structures the character of which depends on time. Specifically, acute amatoxin intoxication produces the well apparent clinical picture within 6 days after intake of the poison. It is characterized by acute renal and hepatic insufficiency in the combination with the injury to the conducting system of heart and the myocrardium itself. Thereafter, the disseminated intravascular coagulation (DIC) syndrome developed accompanied by the signs of progressive tissue hypoxia that ended in death on day 9. The histological study has demonstrated necrotic foci in the liver and oedematous hepatic stroma. Kidneys underwent multiple hemorrhages, necrosis of convoluted tubules and well apparent hydropic protein dystrophy of their epithelium. The adrenal glands showed up signs of necrosis and hemorrhage. It is concluded that poisoning with mushrooms (amatoxin) should be regarded as the most probable cause of the condition requiring differential diagnostics between acute gastroenteritis and renal insufficiency.


Assuntos
Amanita/química , Amanitinas/envenenamento , Rim/patologia , Fígado/patologia , Intoxicação Alimentar por Cogumelos/diagnóstico , Humanos , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos
15.
Presse Med ; 48(7-8 Pt 2): e219-e231, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447333

RESUMO

Image-guided ablation is performed by percutaneously introducing ablation probes to deliver energy into a tumor to destroy it in a controlled and localized fashion. Ablation modalities can be broadly classified as thermal or non-thermal based on the mechanism of tumor destruction and are performed using different types of image guidance for planning, delivering and follow-up of the treatment. Ablation is performed in a minimally invasive fashion, providing greater residual organ preservation with minimal morbidity to the patient. Image-guided ablation is being used in the clinic for the treatment of primary and metastatic tumors, and this article reviews state of the art for the treatment of malignancies in the liver, lung, kidney and musculoskeletal tissue.


Assuntos
Ablação por Cateter/métodos , Neoplasias/cirurgia , Cirurgia Assistida por Computador/métodos , Ablação por Cateter/efeitos adversos , Tecido Conjuntivo/patologia , Tecido Conjuntivo/cirurgia , Humanos , Rim/patologia , Rim/cirurgia , Fígado/patologia , Fígado/cirurgia , Pulmão/patologia , Pulmão/cirurgia , Sistema Musculoesquelético/patologia , Sistema Musculoesquelético/cirurgia , Neoplasias/diagnóstico , Neoplasias/patologia , Especificidade de Órgãos , Complicações Pós-Operatórias/etiologia , Cirurgia Assistida por Computador/efeitos adversos , Resultado do Tratamento
16.
Adv Exp Med Biol ; 1165: 17-36, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399959

RESUMO

With continuing damage, both the indigenous cells of the cortex and medulla, and inflammatory cells are involved in the formation and development of renal fibrosis. Furthermore, interactions among the glomerular, tubular, and interstitial cells contribute to the process by excessive synthesis and decreased degradation of extracellular matrix. The morphology of kidney is different from pathological stages of diseases and changes with various causes. At the end stage of the disease, the kidneys are symmetrically contracted with diffuse granules. Most glomeruli show diffuse fibrosis and hyaline degeneration, and intervening tubules become atrophied. Renal interstitium shows obvious hyperplasia of fibrous tissues with marked infiltration of lymphocytes, mononuclear cells, and plasma cells. The renal arterioles are wall thickening frequently because of hyaline degeneration. Morphologic analysis based on Masson staining of the kidney tissues has been regarded as the golden standard to evaluate the visual fibrosis. However, the present studies have found that the evaluation system has poor repeatability. Several computer-aided image analysis techniques have been used to assess interstitial fibrosis. It is possible that the evaluation of renal fibrosis is carried out by the artificial intelligence renal biopsy pathological diagnosis system in the near future.


Assuntos
Nefropatias/patologia , Rim/patologia , Biópsia , Fibrose , Humanos , Glomérulos Renais/patologia
17.
Adv Exp Med Biol ; 1165: 37-47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399960

RESUMO

Arterial hypertension remains to be a serious problem with considerable morbidity and mortality worldwide in the present age. Hypertension is a major risk factor for cardiovascular diseases such as stroke, myocardial infarction, renal failure, and heart failure. Hypertensive nephropathy is the second leading cause of death in chronic kidney disease (CKD) around the world. Long-time hypertension loading results in renal interstitial fibrosis, which is associated with aberrant activation of renal fibroblasts and excessive generation of extracellular matrix (ECM) proteins. Increasing evidence supported that proteinuria, tubular hypertrophy, oxidative stress, activation of renin-aldosterone-angiotensin system (RAAS), collagen turnover, chronic inflammation, and vasoactive substances synergistically contributed to the pathogenesis of hypertensive renal fibrosis. However, the mechanisms involving the pathogenesis of hypertensive renal fibrosis are complex and not fully understood. Also, the effective clinical therapy to halt or even reverse renal fibrosis in hypertension is still limited. In this chapter, we aimed to provide an overview of the main pathophysiologic and mechanistic features of renal fibrosis under hypertensive state. The completion of the studies in these directions would improve our understanding of renal fibrosis in hypertension and also help us better screen treatment strategies for preventing renal destruction associated with hypertension.


Assuntos
Hipertensão/complicações , Nefropatias/complicações , Fibrose , Humanos , Hipertrofia , Rim/patologia , Estresse Oxidativo , Proteinúria , Sistema Renina-Angiotensina
18.
Adv Exp Med Biol ; 1165: 49-79, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399961

RESUMO

Diabetic nephropathy (DN) is a common kidney disease in people with diabetes, which is also a serious microvascular complication of diabetes and the main cause of end-stage renal disease (ESRD) in developed and developing countries. Renal fibrosis is a finally pathological change in DN. Nevertheless, the relevant mechanism of cause to renal fibrosis in DN is still complex. In this review, we summarized that the role of cell growth factors, epithelial-mesenchymal transition (EMT) in the renal fibrosis of DN, we also highlighted the miRNA and inflammatory cells, such as macrophage, T lymphocyte, and mastocyte modulate the progression of DN. In addition, there are certain other mechanisms that may yet be conclusively defined. Recent studies demonstrated that some of the new signaling pathways or molecules, such as Notch, Wnt, mTOR, Epac-Rap-1 pathway, may play a pivotal role in the modulation of ECM accumulation and renal fibrosis in DN. This review aims to elucidate the mechanism of renal fibrosis in DN and has provided new insights into possible therapeutic interventions to inhibit renal fibrosis and delay the development of DN.


Assuntos
Nefropatias Diabéticas/fisiopatologia , Rim/patologia , Transição Epitelial-Mesenquimal , Fibrose , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Macrófagos , Mastócitos , MicroRNAs , Transdução de Sinais , Linfócitos T
19.
Adv Exp Med Biol ; 1165: 81-100, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399962

RESUMO

Polycystic kidney disease (PKD) is a common genetic disorder characterized by formations of numerous cysts in kidneys and most caused by PKD1 or PKD2 mutations in autosomal dominant polycystic kidney disease (ADPKD). The interstitial inflammation and fibrosis is one of the major pathological changes in polycystic kidney tissues with an accumulation of inflammatory cells, chemokines, and cytokines. The immune response is observed across different stages and occurs prior to or coincident with cyst formation in ADPKD. Evidence for inflammation as an important contributor to cyst growth and fibrosis includes increased interstitial macrophages, upregulated expressions of pro-inflammatory cytokines, activated complement system, and activated pathways including NF-κB and JAK-STAT signaling in polycystic kidney tissues. Inflammatory cells are responsible for overproduction of several pro-fibrotic growth factors which promote renal fibrosis in ADPKD. These growth factors trigger epithelial mesenchymal transition and myofibroblast/fibrocyte activation, which stimulate the expansion of extracellular matrix (ECM) including collagen I, III, IV, V, and fibronectin, leading to renal fibrosis and reduced renal function. Besides, there are imbalanced ECM turnover regulators which lead to the increased ECM production and inadequate degradation in polycystic kidney tissues. Several fibrosis associated signaling pathways, such as TGFß-SMAD, Wnt, and periostin-integrin-linked kinase are also activated in polycystic kidney tissues. Although the effective anti-fibrotic treatments are limited at the present time, slowing the cyst expansion and fibrosis development is very important for prolonging life span and improving the palliative care of ADPKD patients. The inhibition of pro-fibrotic cytokines involved in fibrosis might be a new therapeutic strategy for ADPKD in the future.


Assuntos
Rim/patologia , Doenças Renais Policísticas/fisiopatologia , Proteínas do Sistema Complemento , Citocinas , Matriz Extracelular , Fibrose , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Macrófagos , Rim Policístico Autossômico Dominante , Transdução de Sinais
20.
Adv Exp Med Biol ; 1165: 101-116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399963

RESUMO

Kidney transplantation is a life-change measurement for the patients of end-stage renal disease (ESRD). However, the renal allograft cannot avoid initial acute kidney injury (AKI) and subsequent chronic allograft dysfunction (CAD), gradually develops fibrosis and eventually loses function. It is imperative to disclose the pathogenesis of AKI and CAD in order to facilitate interventions. We have studied the involvement of immunity, inflammation, and apoptosis in ischemia-reperfusion injury (IRI) and/or immunosuppressant induced AKI models, with associated chronic damage. Our research mainly focused on tubular epithelial cells (TECs) that are passive victims and also active participators in injury and mediate following repair or fibrosis. Targeting not only fibroblasts/myofibroblasts, but also TECs, might be a fundamental strategy to prevent and treat renal fibrosis. We have also evaluated the potential application of siRNA targeting caspase-3 and tissue protective erythropoietin derivatives, HBSP and CHBP, aiming to treat AKI and prevent CAD. Significant improvements have been obtained, but timely diagnosis and precise therapy of AKI and prevention of CAD progressing to ESRD are still very challenging. Modern technologies such as microarray and sequencing analysis have been used to identify biomarkers and potentially facilitate individual cell target treatment for transplant patients.


Assuntos
Lesão Renal Aguda , Transplante de Rim/efeitos adversos , Rim/patologia , Traumatismo por Reperfusão , Aloenxertos , Apoptose , Células Epiteliais/citologia , Fibrose , Humanos , Imunidade , Inflamação , Túbulos Renais/citologia
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