Glycolytic enzyme PFKFB3 regulates sphingosine 1-phosphate receptor 1 in proangiogenic glomerular endothelial cells under diabetic condition.

Glomerular angiogenesis is a characteristic feature of diabetic nephropathy (DN). Enhanced glycolysis plays a crucial role in angiogenesis. The present study was designed to investigate the role of glycolysis in glomerular endothelial cells (GECs) in a mouse model of DN. Mouse renal cortex and isolated glomerular cells were collected for single-cell and RNA sequencing. Cultured GECs were exposed to high glucose in the presence (proangiogenic) and absence of a vascular sprouting regimen. MicroRNA-590-3p was delivered by lipofectamine in vivo and in vitro. In the present study, a subgroup of GECs with proangiogenic features was identified in diabetic kidneys by using sequencing analyses. In cultured proangiogenic GECs, high glucose increased glycolysis and phosphofructokinase/fructose bisphosphatase 3 (PFKFB3) protein expression, which were inhibited by overexpressing miRNA-590-3p. Mimics of miRNA-590-3p also increased receptor for sphingosine 1-phosphate (S1pR1) expression, an angiogenesis regulator, in proangiogenic GECs challenged with high glucose. Inhibition of PFKFB3 by pharmacological and genetic approaches upregulated S1pR1 protein in vitro. Mimics of miRNA-590-3p significantly reduced migration and angiogenic potential in proangiogenic GECs challenged with high glucose. Ten-week-old type 2 diabetic mice had elevated urinary albumin levels, reduced renal cortex miRNA-590-3p expression, and disarrangement of glomerular endothelial cell fenestration. Overexpressing miRNA-590-3p via perirenal adipose tissue injection restored endothelial cell fenestration and reduced urinary albumin levels in diabetic mice. Therefore, the present study identifies a subgroup of GECs with proangiogenic features in mice with DN. Local administration of miRNA-590-3p mimics reduces glycolytic rate and upregulates S1pR1 protein expression in proangiogenic GECs. The protective effects of miRNA-590-3p provide therapeutic potential in DN treatment.NEW & NOTEWORTHY Proangiogenetic glomerular endothelial cells (GECs) are activated in diabetic nephropathy. High glucose upregulates glycolytic enzyme phosphofructokinase/fructose bisphosphatase 3 (PFKFB3) in proangiogenetic cells. PFKFB3 protects the glomerular filtration barrier by targeting endothelial S1pR1. MiRNA-590-3p restores endothelial cell function and mitigates diabetic nephropathy.

Sex differences in cardiovascular risk factors for myocardial infarction.

BACKGROUND: Cardiovascular disease is a leading cause of mortality worldwide. This study investigated the effects of sex on traditional cardiovascular risk factors for remote myocardial infarction in a community. METHODS: A cross-sectional study was performed comprising 20,899 participants who underwent physical examination from 2013 to 2015, including systemic blood pressure and 12-lead electrocardiogram monitoring. Fasting blood samples were collected for blood cell counts and biochemistry tests. Remote myocardial infarction was diagnosed on the basis of electrocardiogram findings. RESULTS: A total of 71 male and 21 female patients aged over 50 years were identified with remote myocardial infarction. In the female cohort, low-density lipoprotein (LDL), total cholesterol (TC), as well as high-density lipoprotein (HDL) were negatively correlated with myocardial infarction after adjusting for age. In the male cohort, after adjusting for age, serum levels of glycated hemoglobin (HbA1c) and fasting glucose were positively correlated with myocardial infarction, but the lipid profile, including low-density lipoprotein (LDL), total cholesterol (TC), and high-density lipoprotein (HDL), was negatively correlated with remote myocardial infarction. CONCLUSION: In the male population, dyslipidemia and abnormal glucose metabolism play a role in myocardial infarction. In the female population, dyslipidemia is independent of glucose metabolism. This study highlights sex differences in the regulation of lipids and glucose metabolism in patients with remote myocardial infarction.

Tolerance induction with donor hematopoietic stem cell infusion in kidney transplantation: a single-center experience in China with a 10-year follow-up.

BACKGROUND: Immunosuppressive therapy after life-saving kidney transplantation increases the risk of infection, cardiovascular diseases, metabolic diseases, and cancer. To date, four centers (three in the USA and one in South Korea) have reported clinical tolerance trials in kidney transplantation. We performed the first Chinese clinical trial in which kidney transplantation was combined with donor hematopoietic stem cell (DHSC) infusion to induce tolerance. This study summarizes the 10-year follow-up results. METHODS: From 2009 to 2017, 11 donor/recipient pairs underwent living-related kidney transplantation combined with DHSC infusion. Two of the pairs were human leukocyte antigen (HLA)-matched, and nine were HLA-mismatched. DHSCs were mobilized using granulocyte colony-stimulating factor (G-CSF) and harvested 1 day before transplantation. The recipients received consecutive total lymphoid irradiation (TLI) for 3 days before kidney transplantation. The induction drug was anti-thymocyte globulin (ATG). DHSCs were infused on days 2, 4, and 6 post surgery. All patients were followed-up until Dec 2019. Routine laboratory examinations, chimerism, biopsies, and mixed lymphocyte reactions were performed. RESULTS: One HLA-matched recipient had 30-50% chimerism, while the other patients had less than 1% chimerism. Recipients had donor-specific hyporesponsiveness (DSH) while sustaining normal reactivity to non-donors in mixed lymphocyte reactions. All recipients were followed up for 717-3,918 days. One recipient lost allograft function, and 10 recipients had stable renal function. None of the 11 recipients developed myelosuppression or graft-versus-host disease (GVHD) post transplantation. Our protocol did not increase the risk of infection. Allograft biopsy confirmed that one patient had mild rejection with Banff grade IA, while the other ten recipients did not develop rejection. Five patients were able to reduce the dose of their immunosuppressive therapy. CONCLUSIONS: Our immune tolerance induction protocol, which used DHSC infusion and TLI, achieved low dose immunosuppression with long-term stable kidney allograft survival in Chinese patients.

Major histocompatibility complexes are up-regulated in glomerular endothelial cells via activation of c-Jun N-terminal kinase in 5/6 nephrectomy mice.

BACKGROUND AND PURPOSE: This study aims to explore the mechanism underlying the up-regulation of major histocompatibility complex (MHC) proteins in glomerular endothelial cells in 5/6 nephrectomy mice. EXPERIMENTAL APPROACH: C57/BL6 mice were randomly allocated to sham-operated (2K) and 5/6 nephrectomy (5/6Nx) groups. Mouse splenic lymphocytes, from either syngeneic or allogeneic background, were injected into 5/6Nx mice after total body irradiation. Human glomerular endothelial cells (HGECs) were cultured for experiments in vitro. Western blots, PCR, immunohistochemical and fluorescent staining were used, along with assays of tissue cytokines, lymphocyte migration and renal function. KEY RESULTS: Four weeks after nephrectomy, expression of both mRNA and protein of MHC II, CD80, and CD86 were increased in 5/6Nx glomerular endothelial cells. After total body irradiation, 5/6Nx mice injected with lymphocytes from Balb/c mice, but not those from C57/BL6 mice, exhibited increased creatinine levels, indicating that allograft lymphocyte transfer impaired renal function. In HGECs, the protein levels of MHC and MHC Class II transactivator (CIITA) were increased by stimulation with TNF-α or IFN-γ, which promoted human lymphocytes movement. These increases were reduced by JNK inhibitors. In the 5/6Nx mice, JNK inhibition down-regulated MHC II protein in glomerular endothelial cells, suggesting that JNK signalling participates in the regulation of MHC II protein. CONCLUSION AND IMPLICATIONS: Chronic inflammation in mice subjected to nephrectomy induces the up-regulation of MHC molecules in glomerular endothelial cells. This up-regulation is reduced by inhibition of JNK signalling.

Global deletion of the RNA decapping enzyme Dcp2 postnatally in male mice results in infertility.

The post-transcriptional regulation of gene expression plays an important role in many essential biological processes. The RNA decapping enzyme Dcp2 is a crucial enzyme involved in RNA degradation. Dcp2 proteins are highly expressed in the testis and brain in adult mice. This study aimed to investigate the in vivo functions of Dcp2. An inducible Dcp2 knockout mouse model was established. No obvious health abnormalities were observed after postnatal global deletion of Dcp2 in male mice. However, Dcp2-deleted male mice were infertile and showed Sertoli cell vacuolization and germ cell degeneration. Dcp2 deletion resulted in testicular atrophy, reduced number of epididymal sperm, and increased apoptosis in seminiferous tubules. However, spermatocyte-specific deletion of Dcp2 did not compromise the fertility. The findings of this study indicated that Dcp2 was important for spermatogenesis and male fertility.

Bioinformatics analyses on the immune status of renal transplant patients, a systemic research of renal transplantation.

BACKGROUND: Kidney transplantation is the most effective treatment for end-stage renal disease. Allograft rejections severely affect survivals of allograft kidneys and recipients. METHODS: Using bioinformatics approaches, the present study was designed to investigate immune status in renal transplant recipients. Fifteen datasets from Gene Expression Omnibus (GEO) were collected and analysed. Analysis of gene enrichment and protein-protein interactions were also used. RESULTS: There were 40 differentially expressed genes (DEGs) identified in chronic rejection group when compared with stable recipients, which were enriched in allograft rejection module. There were 135 DEGs identified in acute rejection patients, compared with stable recipients, in which most genes were enriched in allograft rejection and immune deficiency. There were 288 DEGs identified in stable recipients when compared to healthy subjects. Most genes were related to chemokine signalling pathway. In integrated comparisons, expressions of MHC molecules and immunoglobulins were increased in both acute and chronic rejection; expressions of LILRB and MAP 4 K1 were increased in acute rejection patients, but not in stable recipients. There were no overlapping DEGs in blood samples of transplant recipients. CONCLUSION: By performing bioinformatics analysis on the immune status of kidney transplant patients, the present study reports several DEGs in the renal biopsy of transplant recipients, which are requested to be validated in clinical practice.

Successful orthotopic uterine allotransplantation in a rabbit model using aorta and cava anastomoses: a short-term viability study.

PURPOSES: We aim to develop a rabbit model system for studies on uterus transplantation. METHODS: Six sexually mature female New Zealand white rabbits of proven fertility were used for harvesting the uterine allograft with an aortic-caval macrovascular patch (including the aorta, inferior vena cava, common and internal iliacs, and uterine arterial and venous tree). The patches were transplanted in the six recipients orthotopically using aorta and cava anastomoses. Tacrolimus (0.5 mg twice daily, p.o.) was administered postoperatively for immunosuppression. RESULTS: Surgical survival was 100% (n = 6), and the graft survival rate was 83.3% (n = 5). No rabbits died intraoperatively, but only one achieved short-term survival (for 8 days). Four rabbits (#1, #2, #3 and #4) died within the first 24 h as a result of veno-vena anastomosis breakdown, bradycardia, intestinal necrosis, and respiratory failure, respectively. Rabbits #5 (30 h) and #6 (8 days) died from intestinal obstruction and pneumonia, respectively. Uterine morphology was normal in rabbit #6, and rejection was not observed in the grafted uterus, which was further verified by H&E and immunohistochemistry. CONCLUSIONS: Aorta and cava anastomoses can be used to ensure a viable transplanted uterus by reconstructing an adequate blood supply to the transplanted uterine graft in a rabbit model. We have demonstrated the feasibility of tacrolimus monotherapy in suppressing the rejection of an allotransplanted uterus in a rabbit model. However, UTx in a rabbit model seems difficult to achieve long-term survival.

MicroRNA-141-3p/200a-3p target and may be involved in post-transcriptional repression of RNA decapping enzyme Dcp2 during renal development.

The RNA decapping enzyme Dcp2 is a crucial enzyme involved in the process of RNA turnover, which can post-transcriptionally regulate gene expression. Dcp2 has been found to be highly expressed in embryonic, but not adult, kidneys. Here we showed that Dcp2 mRNA was expressed, but Dcp2 proteins were absent, in mouse kidneys after postnatal day 10 (P10). In kidneys of adult Dcp2-IRES-EGFP knock-in mice, Dcp2 was undetectable but EGFP was expressed, indicating that Dcp2 mRNA was not completely silenced in adult kidneys. Using luciferase reporter assays, we found that miR-141-3p/200a-3p directly targeted the 3' UTR of Dcp2 mRNA. Overexpression of miR-141-3p and miR-200a-3p downregulated endogenous Dcp2 protein expression. Furthermore, miR-141-3p and miR-200a-3p expression was low in embryonic kidneys but increased dramatically after P10 and was negatively correlated with Dcp2 protein expression during renal development. These results suggest miR-141-3p/200a-3p may be involved in post-transcriptional repression of Dcp2 expression during renal development. ABBREVIATIONS: IRES: internal ribosome entry site; EGFP: enhanced green fluorescent protein; UTR: untranslated region.

Dynamic change of glomerular filtration rate in the early stage is associated with kidney allograft status: a preliminary report.

BACKGROUND: This study aimed to investigate the relationship between the dynamic changes of estimated glomerular filtration rate (eGFR) in the early stage post renal transplantation and renal allograft dysfunction. METHODS: We selected 9 patients with interstitial fibrosis and tubular atrophy (IF/TA) and 11 patients with stable renal function based on the Banff 2007 classification system. Pathology of the patients was evidenced with renal biopsy results. Glomerular filtration rate (GFR) was calculated continuously for 14 days post-transplantation by using an estimated GFR (eGFR) formula adjusted into Chinese. Linear regression was employed, and eGFR slopes were compared. Prisoners or organs from prisoners were not used in this study. RESULTS AND CONCLUSION: The eGFR slope in the IF/TA group was significantly higher than that in the stable group (P < 0.01), and a cut-off value of 5.11 mL/min/1.73 m(2)/d was a reliable clinical value in a receiver operating characteristic (ROC) curve. On the basis of the ROC area under the curve, predictive accuracy of the eGFR slope was excellent (0.848). In conclusion, the eGFR in IF/TA increased faster within a period of 14 days post-transplantation, suggesting that reperfusion in the early stage may damage the glomerular filtration membrane to some extent. Furthermore, reperfusion might adversely affect long-term renal allograft survival.

miRNA-1297 induces cell proliferation by targeting phosphatase and tensin homolog in testicular germ cell tumor cells.

To investigate the role of miR-1297 and the tumor suppressor gene PTEN in cell proliferation of testicular germ cell tumors (TGCT). MTT assays were used to test the effect of miR-1297 on proliferation of the NCCIT testicular germ cell tumor cell line. In NCCIT cells, the expression of PTEN was assessed by Western blotting further. In order to confirm target association between miR-1297 and 3'-UTR of PTEN, a luciferase reporter activity assay was employed. Moreover, roles of PTEN in proliferation of NCCIT cells were evaluated by transfection of PTEN siRNA. Proliferation of NCCIT cells was promoted by miR-1297 in a concentration-dependent manner. In addition, miR-1297 could bind to the 3'-UTR of PTEN based on luciferase reporter activity assay, and reduced expression of PTEN at protein level was found. Proliferation of NCCIT cells was significantly enhanced after knockdown of PTEN by siRNA. miR-1297 as a potential oncogene could induce cell proliferation by targeting PTEN in NCCIT cells.

Combination of Total Lymphoid Irradiation, Low-Dose IVIG and ATG as Rescue Therapy for Highly Sensitized and Antibody-Mediated Rejection Renal Transplant Recipients.

UNLABELLED: Background: It is now clear that antibody- mediated rejection (AMR) is a major cause of graft failure. To avoid AMR, transplantation is preferably performed in non- or low-sensitized patients. For patients with pre-existing HLA antibodies due to pre-transplant sensitization or those with de novo HLA antibodies due to transplantation, elimination or reduction of HLA antibodies becomes critical to prevent AMR. Materials and Methods: In this clinical trial, we test the efficacy of a combination therapy of total lymphoid irradiation (TLI), low- dose intravenous immunoglobulin (IVIG), and anti-thymocyte globulin (ATG) with or without plasmapheresis (PP) in treating patients with HLA antibodies. Thirteen HLA antibody positive patients receiving renal transplants during 2009-2011 were enrolled in this study. Two cases with pre-existing HLA antibodies received combined therapy of TLI, PP, low-dose IVIG, and ATG induction. Eleven cases with de novo HLA antibodies and biopsy-proven AMR received TLI, low-dose IVIG, and ATG with or without PP. RESULTS: Two sensitized patients with pre-existing HLA antibodies were successfully desensitized and able to accept renal transplantation without an observable AMR episode in 12 months of post-transplant follow-up. In 11 AMR cases with de novo HLA antibodies, only one patient failed to respond to the therapy and lost the allograft. In the other ten cases, the follow-up biopsies at one year post transplant showed no evidence of rejection and the patients had stable renal function. B cell proliferation was persistently inhibited in both desensitization and AMR patients. CONCLUSIONS: Combined therapy of TLI, PP, low-dose IVIG, and ATG is an effective therapeutic measure to reduce the level of HLA antibodies and therefore to desensitize recipients pre-transplant and to reverse AMR post transplant. The potential mechanism of the therapy involves inhibition of B cell proliferation.

Helix B surface peptide administered after insult of ischemia reperfusion improved renal function, structure and apoptosis through beta common receptor/erythropoietin receptor and PI3K/Akt pathway in a murine model.

Erythropoietin (EPO) has been well recognized as a tissue protective agent by inhibiting apoptosis and inflammation. The tissue protective effect of EPO, however, only occurs at a high dosage, which may elicit severe side-effects at the meantime. Helix B surface peptide (HBSP), a novel peptide derived from the non-erythropoietic helix B of EPO, plays a specific role in tissue protection. We investigated effects of HBSP and the expression of its heterodimeric receptor, beta common receptor (ßcR)/EPO receptor ( ), in a murine renal ischemia reperfusion (IR) injury model. HBSP significantly ameliorated renal dysfunction and tissue damage, decreased apoptotic cells in the kidney and reduced activation of caspase-9 and -3. The ßcR/EPOR in the kidney was up-regulated by IR, but down-regulated by HBSP. Further investigation revealed that the expression and phosphorylation of Akt was dramatically enhanced by HBSP, but strongly reversed by wortmannin, the PI3K inhibitor. Wortmannin intervention improved ßcR/EPOR expression, promoted caspase-9 and -3 activation, and increased active caspase-3 positive cells, while renal function and structure, and apoptotic cell counts scarcely changed. This result indicates a significant contribution of PI3K/Akt signaling pathway in the renoprotection of HBSP. The therapeutic effects of HBSP in this study suggest that HBSP could be a better candidate for renal protection.

Osteopontin level correlates with acute cellular renal allograft rejection.

BACKGROUND: Osteopontin (OPN) is a potent proinflammatory cytokine that is upregulated in cell-mediated immunity and various inflammatory states of the kidney. However, the relationship between OPN levels plasma/urine and acute renal allograft rejection is still unknown. Therefore, we assessed the relationship between OPN levels in plasma/urine and acute cellular rejection post-renal transplantation. MATERIALS AND METHODS: Clinical data and biologic samples of renal transplant recipients were analyzed retrospectively. Patients with biopsy-proved acute cellular rejection (ACR) (n = 22), protocol biopsy-proved non-rejection (non-R) (n = 16), and living related donors as healthy control (HC) (n = 10) were involved in this study. OPN level in plasma and urine was detected using the human OPN enzyme-linked immunosorbent assay kit. Type and grade of ACR were diagnosed based on Banff' 03 classification criteria of renal allograft pathology. No prisoners or organs from prisoners were used in this study. RESULTS: Compared with non-R patients and HC, plasma and urine OPN levels in ACR patients were significantly increased (P < 0.05), whereas there was no significant difference between non-R patients and HC (P > 0.05). In ACR patients, plasma OPN level was positively correlated with Banff grading of acute rejection, and a cut-off value of 24.20 ng/mL was further demonstrated a good clinical value in receiver operation characteristic curve. CONCLUSIONS: The data obtained suggested that assessment of OPN levels in plasma and urine, especially in plasma, should be useful in predicting and evaluating the severity of ACR in renal transplant recipients.

Naked caspase 3 small interfering RNA is effective in cold preservation but not in autotransplantation of porcine kidneys.

BACKGROUND: Caspase 3 associated with apoptosis and inflammation plays a key role in ischemia-reperfusion injury. The efficacy of naked caspase 3 small interfering RNA (siRNA) has been proved in an isolated porcine kidney perfusion model but not in autotransplantation. MATERIALS AND METHODS: The left kidney was retrieved from mini pigs and infused with the University of Wisconsin solution with or without 0.3mg of caspase 3 siRNA into the renal artery with the renal artery and vein clamped for 24-h cold storage (CS). After right nephrectomy, the left kidney was autotransplanted into the right for 48 h without systemic treatment of siRNA. RESULTS: Fluorescent dye-labeled caspase 3 siRNA was visualized in the post-CS kidneys but was weakened after transplantation. The expression of caspase 3 messenger RNA and precursor was downregulated by siRNA in the post-CS kidneys. In the siRNA-preserved posttransplant kidneys, however, the caspase 3 messenger RNA and active subunit were upregulated with further decreased precursor but increased active caspase 3+ cells, apoptotic cells, and myeloperoxidase+ cells. Moreover, the renal tissue damage was aggravated by siRNA, whereas the renal function was not significantly changed. CONCLUSIONS: Naked caspase 3 siRNA administered into the kidney was effective in cold preservation but not enough to protect posttransplant kidneys, which might be because of systemic complementary responses overcoming local effects.

Mycophenolate mofetil inhibits macrophage infiltration and kidney fibrosis in long-term ischemia-reperfusion injury.

Immunosuppressants have been widely used in renal transplantation, in which ischemia-reperfusion injury is inevitable. Mycophenolate mofetil (MMF) is a relative novel immunosuppressant and also attenuates ischemia-reperfusion injury in the acute phase, but its long-term effects are still obscure. Unilateral renal ischemia-reperfusion injury model was established in Sprague-Dawley rats and 30 mg/kg/day MMF or natural saline was administered a day before the surgery. Renal function was monitored, and histological changes and fibrosis in the kidney were evaluated in both short and long terms. TGF-ß1 secretion and MCP-1 expression were determined by immunohistochemistry and real-time PCR respectively. The infiltration of macrophages in renal tissues was also assessed by fluorescence activated cell sorting (FACS). MMF treatment significantly improved renal function in ischemia-reperfusion injury rats in the short and long-term and also effectively prevented interstitial fibrosis. TGF-ß1 secretion and MCP-1 expression in the renal tissue of MMF-treated rats were much lower than those in natural saline-treated rats, with much less macrophage infiltration as well. MMF treatment effectively prevented the deterioration of renal function and interstitial fibrosis in ischemia-reperfusion injury rats, which may be associated with decreased TGF-ß1, MCP-1 and macrophages. These results provide evidence for the choice of MMF in the renal transplant patients not only for acute renal injury but also for long-term survival of renal allograft.

Erythropoietin ameliorates renal ischemia and reperfusion injury via inhibiting tubulointerstitial inflammation.

BACKGROUND: Tubulointerstitial inflammation is the characteristics of renal ischemia reperfusion injury (IRI) that is inevitable in kidney transplantation. Erythropoietin (EPO) has recently been shown to have protective effects on renal IRI by anti-apoptosis and anti-oxidation. Here, the effect and mechanism of EPO on renal IRI were further investigated, with a focus on tubulointerstitial inflammation. MATERIALS AND METHODS: Male Sprague-Dawley rats were administrated with saline or EPO prior to IRI induced by bilateral renal pedicle clamping. Twenty-four hours following reperfusion, the effects of EPO on renal IRI were assessed by renal function and structure, tubulointerstitial myeloperoxidase (MPO) positive neutrophils, and proinflammatory mediator gene expression. The translocation and activity of NF-κB in renal tissues were also evaluated. RESULTS: Compared with control groups, the EPO treated group exhibited lower serum urea and creatinine levels, limited tubular necrosis with a lower score of renal histological lesion. MPO positive cells in the tubulointerstitial area were greatly increased by IRI, but significantly reduced by the treatment of EPO. The gene expression of proinflammatory cytokines (IL-1ß, IL-6, IL-10, and TNF-α) and chemokine (MCP-1) was also significantly decreased by EPO. In addition, less activation and nuclear-translocation of NF-κB was observed in the kidney treated by EPO as well. CONCLUSION: EPO improved renal function and structure in IRI rats via reducing neutrophils in the tubulointerstitium, the production of proinflammatory cytokines and chemokine, as well as the activation and nuclear-translocation of NF-κB. EPO may have potential clinical applications as an anti-inflammation agent clinically for a wide range of injury.

[Analysis of microchimerism in living renal transplantation between mothers and children relationship].

OBJECTIVE: To compare the microchimerismic and rejection rates in living donor kidney transplant recipients in mother and child relations and other relations. METHODS: This retrospective single-center study enrolled 130 recipients to receive allografts from living related donors from 2004 to 2008 at our hospital. They were followed up for 1 - 5 years. The demographic data of the study population were analyzed by basic statistical methods. A total of 43 recipient blood samples were collected for the detection of microchimerism by the assays of short tandem repeat (STR) and sex-determining region-y gene (SRY) polymerase chain reaction (PCR). RESULTS: The 1-year patient/graft survival rates were 93.8% and 92.3% respectively. And there was no significant differences between mother and child group and other relative group. Forty-six biopsy samples were collected from 46 recipients. Twenty-six (20.0%) cases had the occurrences of acute rejection episodes in different Banff degrees as proven by biopsy. 53.8% (14/26) cases were mother and child renal transplantation, higher than other relative (46.2%, 12/26). The mother donor kidney transplant recipients had about a twice higher rejection rate (30.4% vs 14.3%, P = 0.028) and a twice higher microchimerismic rate (25.0% vs 14.8%) than other relative. CONCLUSION: Compared with other relations, the mother donor kidney recipients tend to have higher rates of microchimerism and acute rejection. And the special immune effect in mothers and children renal transplantation may influence its outcomes.

Analysis of transcriptional factors and regulation networks in patients with acute renal allograft rejection.

Acute rejection (AR) remains a major clinical challenge, leading to the development of chronic renal allograft failure. The aim of the present study was to explore potential transcriptional factors and regulation networks in the disease to predict the occurrence and process of AR and understand potential strategies to prevent from the disease. Three-hundred fifty-two patients with renal failure had kidney transplantation during March 2006 and March 2010, of which 85 suffered from AR. Plasma from 13 patients with kidney transplantation was collected, of which 5 were from patients with AR and 8 from those without AR. Among the 179 proteins identified by using iTRAQ labeling and quantitative proteomic technology, 66 proteins were at least 2-fold different between patients with or without AR. The results demonstrated that the dominant processes and responses were associated with inflammation and complement activation in AR. A number of transcription factors were identified in AR patients, including nuclear factor-κB, signal transducer and activator of transcription 1, signal transducer and activator of transcription 3. The analysis of transcription regulation networks suggested that the cross-talks among these key transcription factors might contribute to the acute response and coagulation pathway. Thus, our study provides a new description and insight into the molecular events in AR and potential strategies for identifying diagnostic biomarkers.

[Preliminary exploration in proteomic-based mechanistic analysis of patients with acute renal allograft rejection].

OBJECTIVE: To explore the application of proteomics in the mechanistic analysis of acute rejection (AR). METHODS: Quantified proteomics with isobaric tags for relative and absolute quantitation (iTRAQ) labeling was utilized to identify the protein profiling between the transplantation patients with (n = 5) or without AR (n = 8) from 2008 to 2010. RESULTS: Among the 179 identified proteins, 66 proteins in AR patients had at least a 2-fold change as compared with those without AR. The results demonstrated the dominant processes and responses associated with inflammation and complement activation. It was consistent with the underlying immune rejection associated with AR. Moreover, the results also indicated that high-coagulation state existed in AR patients. A number of transcription factors were identified in AR patients, including nuclear factor-κB, signal transducer and activator of transcription 1, signal transducer and activator of transcription 3. The analysis of transcription regulation networks suggested that the cross-talks among these key transcription factors might play an important role in the acute response and activation of coagulation system. CONCLUSION: The application of proteomics provides a new strategy of mechanistic analysis in AR.