Lupus-like manifestations after allogenic hematopoietic stem cell transplantation: a rare case of chronic graft-versus-host disease.

Chronic graft-versus-host disease (GvHD) is the leading cause of late death in allogenic hematopoietic stem cell transplantation recipients, of which the kidney is a potential target. In this article, we report an extremely rare case of chronic GvHD, characterized by immune complex-mediated diffuse proliferative glomerulonephritis and various autoantibodies detected in the serum; it is the first case of lupus-like chronic GvHD reported to date. The patient responded well to intensive immunosuppressive therapy and reached complete remission. Mycophenolate mofetil was more effective than tacrolimus in this case, suggesting that treatment of kidney diseases associated with chronic GvHD should be based on pathogenesis and pathological patterns.

Rituximab may affect T lymphocyte subsets balance in primary membranous nephropathy.

BACKGROUND: The aim of this study was to investigate the effects and significance of rituximab (RTX) on the levels of T lymphocyte subsets in patients diagnosed with primary membranous nephropathy (PMN). METHODS: A total of 58 PMN patients and 25 healthy donors were chosen as the subjects. Among the PMN patients, 40 individuals received RTX treatment and completed at least 6 months of follow-up. All subjects underwent flow cytometry analysis to determine the peripheral blood lymphocyte subsets. The changes in anti-PLA2R antibody titers and 24-hour urinary protein levels were evaluated by ELISA and Biuret method before and after treatment. RESULTS: (1) The PMN group exhibited a significantly greater percentage of peripheral blood CD3-CD19+ B cells than the healthy group, which is consistent with the findings of previous reports. Additionally, compared with those in the peripheral blood of healthy individuals, the numbers of CD4+ central memory T cells, CD4+ effector memory T cells, CD4+/CD8+, and CD4+CD25+ T cells in the PMN peripheral blood were markedly greater. However, the number of peripheral blood Treg cells was reduced in the PMN group. (2) After 6 months of RTX treatment, PMN patients exhibited significant decreases in anti-PLA2R antibody titers, 24-hour urinary protein levels, and peripheral blood CD3-CD19+ B cells. Importantly, RTX administration decreased CD4+CD25+ T cells and CD4+/CD8+ in the peripheral blood of PMN patients and improved Treg cell levels. (3) RTX treatment induced alterations in the CD4+ T lymphocyte subsets in PMN patients, which did not correlate with B lymphocyte counts or anti-PLA2R antibody titers. CONCLUSIONS: RTX treatment might have a beneficial impact on cellular immunity by effectively restoring the balance of CD4+ T lymphocyte subsets in PMN patients, which is beyond its effects on B cells and antibody production. TRIAL REGISTRATION: The research was registered at the First Affiliated Hospital of Soochow University. REGISTRATION NUMBER: MR-32-23-016211. Registration Date: May 31, 2023.

Clinical study on the correlation between monocyte-related ratios and calcification of the abdominal aorta in peritoneal dialysis patients.

INTRODUCTION: We aimed to investigate the relationship between monocyte/lymphocyte ratio (MLR) and monocyte/high-density lipoprotein ratio (MHR) with abdominal aortic calcification (AAC) in patients on peritoneal dialysis (PD). METHODS: The time-averaged (TA) of relevant indexes and AAC scores (AACs) of 160 eligible patients were measured. RESULTS: Patients divided into the new AAC (n = 57) and the other without (n = 82). High TA-MLR (OR = 110.537, p = 0.018) and long duration of dialysis (OR = 1.045, p < 0.001) were independent risk factors of the new AAC. Patients divided into the no AAC (n = 82), the moderate-to-severe AAC (n = 26), and the mild AAC (n = 52). High TA-MLR (OR = 42.649, p = 0.032), high age at starting PD (OR = 1.055, p < 0.001), and long duration of PD (OR = 1.036, p < 0.001) were independent risk factors of AAC severity. CONCLUSIONS: MLR is an independent risk factor for the occurrence and severity of AAC and its value for the assessment of AAC is better than MHR.

Upregulation of FABP7 inhibits acute kidney injury-induced TCMK-1 cell apoptosis via activating the PPAR gamma signalling pathway.

Acute kidney injury (AKI) is a frequently seen critical disorder in the clinic. The current research aimed to examine the role of hydroxyacid oxidase 2 (FABP7) in AKI-induced cell apoptosis. A total of 289 overlapping genes were used to perform gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and to construct a protein-protein interaction (PPI) network using the DAVID database and Cytoscape software. The 10 hub genes of the PPI network were screened out using the cytohubba plug-in of Cytoscape software. FABP7 represented both the differentially expressed gene (DEG) from the GSE44925 and GSE62732 datasets and the top hub gene of the PPI network. The results of the PAS assay showed that FABP7 knockout in vivo aggravated lipopolysaccharide (LPS)-induced AKI. Meanwhile, LPS inhibited cell viability and the expression of FABP7, PPARγ, PPARα, PTEN and p27kip1, and increased the TNF-α level, and cleaved caspase-3/-9 expression and the phosphorylation of PTEN in vitro. FABP7 overexpression reversed the effects of LPS on inhibiting cell viability and proliferation, promoting cell apoptosis, increasing the expression of FABP7, PPARγ, PTEN and p27kip1, and reducing cleaved caspase-3/-9 expression and the phosphorylation of PTEN, but had no influence on PPARα expression. The PPARγ signal pathway inhibitors blocked the protective effect of FABP7 overexpression in LPS-treated TCMK-1 cells, while the PPARγ signal pathway activator inhibited the harmful effect of FABP7 inhibition in LPS-treated TCMK-1 cells. In conclusion, FABP7 overexpression inhibited the AKI-induced cell apoptosis and promoted the proliferation through activating the PPARγ signal pathway in vivo and in vitro.

miR-19a-3p targets cell adhersion molecule 2 to inhibit proliferation and metastasis of renal carcinoma 7867-O cells via blockingAKT pathway / 中国肿瘤生物治疗杂志

@# Objective: To explore the mechanism of miR-19a-3p regulating cell adhesion molecule 2 (CADM2) to inhibit the proliferation and metastasis of renal carcinoma cells via the AKT signaling pathway. Methods: A total of 42 patients with renal cancer admitted to Department of Nephrology, the First Affiliated Hospital of Suzhou University from April 2012 to November 2017 were enrolled to collect samples of surgically resected renal carcinoma tissues and paracancerous tissues. Expression of miR-19a-3p was detected in renal carcinoma tissues and 4 types of renal carcinoma cell lines such as 786-O by quantitative Real-time polymerase chain reaction (qPCR). The effects of miR-19a-3p knockdown on proliferation, invasion and epithelial mesenchymal transition (EMT) of renal carcinoma 786-O cells were evaluated by CCK-8 assay, Transwell assay and immunofluorescence, respectively. Subsequently, dual luciferase reporter assay was used to verify whether CADM2 was a target gene of miR-19a-3p. Furthermore, Wb was applied to detect the regulatory effect of miR-19a-3p onAKT signaling pathway through CADM2. Results: miR-19a-3p expression was significantly up-regulated in renal carcinoma tissues and cell lines (all P<0.01). Knockdown of miR-19a-3p could inhibit proliferation, invasion and EMT process of 786-O cells; furthermore, the results indicated that CADM2 was a direct target of miR-19a-3p and its expression was down-regulated (P <0.05 or P<0.01). Additionally, knockdown of miR-19a-3p obviously suppressed proliferation, migration and EMT process of 786-O cells via up-regulating CADM2 and blocking AKT pathway (all P<0.05 or P<0.01), thus alleviating the occurrence and development of renal carcinoma. Conclusion: The study demonstrates that miR-19a-3p has a high expression level in renal carcinoma tissues; knockdown of miR-19a-3p could significantly inhibit the proliferation, migration and EMT process of renal carcinoma tissues, and its mechanism may be associated with miR-19a-3p/CADM2/AKT axis.

Prevention of contrast-induced nephropathy with prostaglandin E1 in patients undergoing percutaneous coronary procedures: A meta-analysis of 24 randomized controlled trials
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BACKGROUND: Contrast-induced nephropathy (CIN) is the third most common cause of acute kidney injury in hospitalized patients. There have been many conflicting results across trials that have evaluated the prophylactic efficacy of prostaglandin E1 (PGE1) for prevention of CIN in patients undergoing percutaneous coronary procedures. PGE1 may have renal-protective effects due to its pleiotropic properties. The aim of this study was to evaluate the efficacy of PGE1 in preventing CIN. MATERIALS AND METHODS: We searched PubMed, Embase, Cochrane Library, Chinese Biomedical Literature, China National Knowledge Infrastructure, VIP Information/Chinese Scientific Journals, and WANFANG databases for randomized controlled trials (RCTs) comparing the preventive effects of PGE1 versus controls (conventional hydration, no PGE1, or placebo) on CIN in patients undergoing percutaneous coronary procedures from January 1999 to June 2016. Study characteristics and outcome data were abstracted by two independent reviewers; the risk of bias was also assessed by two reviewers. RESULTS: 24 RCTs involving 3,915 patients were included. Compared with controls, PGE1 reduced the risk of CIN (risk ratio: 0.40, 95% confidence interval (CI): 0.33, 0.48; p < 0.01). Serum creatinine levels in the PGE1 groups were significantly lower than in the control groups at 24, 48, and 72 hours after operation (mean difference (MD): -10.06, 95% CI: -16.94, -3.19; MD: -15.47, 95% CI: -21.75, -9.18; and MD: -11.15, 95% CI: -14.40, -7.91, respectively). Cystatin C was significantly lower for the PGE1 group than the control groups at 24, 48, and 72 hours after operation (MD: -0.24, 95% CI: -0.40, -0.07; MD: -0.34, 95% CI: -0.53, -0.14; and MD: -0.32, 95% CI: -0.49, -0.15, respectively). CONCLUSION: PGE1 may play an important role in reducing the incidence of CIN in patients undergoing percutaneous coronary procedures.
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Long non-coding RNA MALAT1 interacts with transcription factor Foxo1 to regulate SIRT1 transcription in high glucose-induced HK-2 cells injury.

BACKGROUND: Tubular injury is considered as a crucial pathological feature of diabetic nephropathy. LncRNA MALAT1 is involved in diabetic complications. Hence the role of MALAT1 in high glucose-induced renal tubular epithelial cells (HK-2) injury deserves investigation. METHODS: The diabetic mice model was established with streptozotocin (STZ) injection. The expression of NEAT1, SIRT1, and Foxo1 mRNA and protein was determined with qRT-PCR and western blot, respectively. The serum creatinine and urinary albumin were examined by enzyme linked immunosorbent assay (ELISA). Interaction between MALAT1 and Foxo1 was detected with RIP and RNA pull-down assay, respectively. Dual luciferase reporter assay was used to evaluate the binding between Foxo1 and SIRT1. RESULTS: LncRNA MALAT1 was up-regulated in kidney tissues of diabetic mice and in HK-2 cells treated with high glucose, while the expression of SIRT1 was decreased. Interaction between MALAT1 and Foxo1 was observed in HK-2 cells and the interaction was promoted by high glucose treatment. Foxo1 activated SIRT1 transcription by binding to its promoter, and MALAT1 repressed SIRT1 expression through targeting Foxo1. CONCLUSION: LncRNA MALAT1 interacts with transcription factor Foxo1 to represses SIRT1 transcription in high glucose incubated HK-2 cells, which promotes high glucose-induced HK-2 cells injury.

Silencing of CXCL12 performs a protective effect on C5b-9-induced injury in podocytes.

PURPOSE: Podocytes, terminal differentiation cell in glomerulu, are crucial to kidney-related diseases such as membranous nephropathy (MN). MN is characterized by podocyte injury and glomerular basement membrane thickening. This paper focused to investigate the expression of chemokine (C-X-C motif) ligand 12 (CXCL12) in MN patients and its possible role in podocyte injury. METHODS: Through the enzyme-linked immunosorbent assay, CXCL12 level in the serum and urine of MN patients was examined. Further, several assays of cell viability, apoptosis, quantitative real-time PCR and western blot were applied to explore the effects of CXCL12 in the model of podocyte injury. RESULTS: We found a significant increase of CXCL12 in serum and urine of MN patients, which indicated that CXCL12 may be involved in the progression of MN. And in vitro C5b-9-induced podocyte injury model, the proliferation of podocytes was inhibited whereas CXCL12/CXCR4 and phosphorylated STAT3 (p-STAT3) were increased. Silencing of CXCL12 remarkably promoted cell proliferation, inhibited cell apoptosis and suppressed CXCL12/CXCR4, p-STAT3 and caspase 3. Consistently, STAT3 inhibitor and berberine (a CXCL12 antagonist) also reduced CXCL12 treatment-induced apoptosis. CONCLUSIONS: All data suggested that silencing of CXCL12 had a protective effect on podocyte injury, which may be through inhibiting CXCL12/STAT3 signaling pathway.

IL-1ß increases urinary corin in patients with primary proteinuric kidney diseases and in 293 cells.

Corin is a serine protease that is important for the regulation of blood pressure and water balance. Corin was initially discovered in the heart, however, it has also been detected in kidney cells, though its function in the kidneys is unclear. To further investigate the function of corin in the kidney, the present study analyzed the levels of corin in urine and blood samples collected from normal individuals and patients with primary proteinuric diseases. The associations between the levels of corin, and the cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were then assessed. The results demonstrated that corin was detectable in the urine and plasma following an enzyme-linked immunosorbent assay; the level of corin in the urine was associated with the level of urinary ß2-microglobulin (P=0.01), which was indicative of renal tubular injury. When compared with normal individuals, the levels of urinary corin in proteinuric patients were markedly increased (P=0.02), and were also associated with IL-1ß (P=0.03). This correlation between corin and IL-1ß was confirmed in vitro using 293 cells. As the IL-1ß concentrations increased (0, 0.1, 1, 10 ng/ml), an elevation in the level of corin was observed in the culture medium (P<0.01); however, the amount of corin was not markedly altered in the cell lysate (P>0.05). In addition, when TNF-α reached 10 ng/ml, the level of corin in the medium increased significantly when compared with the control group (0 ng/ml; P=0.02), however, no significant difference in corin levels was detected in the cell lysate. The results suggest that the cytokines IL-1ß and TNF-α may increase urinary corin in patients with primary proteinuric kidney diseases. Cytokines may accelerate corin shedding from the cell membrane of renal tubule epithelial cells. These findings indicate that corin may be associated with kidney inflammation and injury.

Long non-coding MIAT mediates high glucose-induced renal tubular epithelial injury.

BACKGROUND AND OBJECTIVE: Long non-coding RNAs (lncRNAs) constitute a novel class of non-coding RNAs that take part in occurrence and development of diabetes complication via regulating gene expression. However, litter is known about lncRNAs in the setting of diabetes induced nephropathy. The aim of this study was to examine whether lncRNA-myocardial infarction-associated transcript (MIAT) is involved in diabetes induced renal tubules injury. METHODS: Adult Wister rats were randomly assigned to receive intraperitoneal STZ (65 mg/kg) to induce diabetes. Rats treated with equal volume of citrate buffer were as control. Renal function was evaluated by analysis of serum creatinine and blood urea nitrogen (BUN) every four weeks after STZ administration. Also tubules of all rats were collected for determination of MIAT and Nrf2 level at the corresponding phase. The in vitro high glucose-triggered human renal tubular epithelial cell line (HK-2) was used to explore the mechanism underling MIAT regulated high glucose-induced tubular damage. RESULTS: In diabetic rats, MIAT showed the lower level and its expression is negatively correlated with serum creatinine and BUN. Consistent with diabetic rat, exposed to high glucose, HK-2 cells expressed lower level of MIAT and Nrf2, and also showed reduction in cell viability. By pcDNA-MIAT plasmid transfection, we observed that MIAT overexpression reversed inhibitory action of Nrf2 expression by high glucose. Moreover, the data of RNA pull-down and RIP showed that MIAT controlled Nrf2 cellular through enhancing Nrf2 stability, which was confirmed by CHX and MG132 administration. Inhibitory effect of cell viability by silencing MIAT was also reversed by Nrf2 overexpression. CONCLUSION: In summary, our data suggested that MIAT/Nrf2 served as an important signaling pathway for high glucose induced renal tubular epithelial injury.

High glucose induces renal tubular epithelial injury via Sirt1/NF-kappaB/microR-29/Keap1 signal pathway.

OBJECTIVE: Diabetic nephropathy (DN) is a serious complication that commonly confronted by diabetic patients. A common theory for the pathogenesis of this renal dysfunction in diabetes is cell injury, inflammation as well as oxidative stress. In this content, the detailed molecular mechanism underlying high glucose induced renal tubular epithelial injury was elaborated. METHODS: An in vivo rat model of diabetes by injecting streptozotocin (STZ) and an in vitro high glucose incubated renal tubular epithelial cell (HK-2) model were used. Expression levels of Keap1, nuclear Nrf2 and p65 were determined by western blotting. Level of microR-29 (miR-29) was assessed using quantitative RT-PCR. Combination of p65 and miR-29 promotor was assessed using chromatin immunoprecipitation. Keap1 3'-UTR activity was detected using luciferase reporter gene assay. Cell viability was determined using MTT assay. RESULTS: In diabetic rat, miR-29 was downregulated and its expression is negatively correlated with both of serum creatinine and creatinine clearance. In high glucose incubated HK-2 cell, deacetylases activity of Sirt1 was attenuated that leads to decreased activity of nuclear factor kappa B (NF-κB). NF-κB was demonstrated to regulate miR-29 expression by directly binding to its promotor. The data of luciferase assay showed that miR-29 directly targets to Keap1 mRNA. While high glucose induced down regulation of miR-29 contributed to enhancement of Keap1 expression that finally reduced Nrf2 content by ubiquitinating Nrf2. Additionally, overexpression of miR-29 effectively relieved high glucose-reduced cell viability. CONCLUSION: High glucose induces renal tubular epithelial injury via Sirt1/NF-κB/microR-29/Keap1 signal pathway.

Down-regulation of miR-186 contributes to podocytes apoptosis in membranous nephropathy.

BACKGROUND AND AIM: Podocytes apoptosis is the key process in the development of membranous nephropathy and miR-186 is reported to be related with cell apoptosis. Here we investigated the expression of miR-186 in membranous nephropathy (MGN) patients and the mechanism underlying the podocytes apoptosis. METHODS: Thirty patients with MGN and 30 healthy people were included in this study. The expression of miR-186 was detected in renal tissue and podocyte cells exposed to AngII by real-time PCR. Caspase-3 activity was used to evaluate podocytes apoptosis. TLR4 and P2×7 protein expression was quantified by western blotting. miR-186 inhibitor and miR-186 mimic were transfected into cells to investigate the mechanism underlying miR-186 in podocytes apoptosis. RESULTS: In MGN patients, the level of miR-186 was significantly down-regulated as well as the protein expression of TLR4 and P2×7 was up-regulated in renal tissue. In vitro experiments, TLR4 siRNA increased the expression of miR-186 and miR-186 inhibitor elevated the mRNA and protein expression of P2×7 in podocytes exposed to AngII. In addition, the level of cleaved-caspase-3 was up-regulated by miR-186 inhibitor. The TUNEL-positive cells and caspase-3 activity of podocytes induced by AngII were down-regulated by miR-186 mimic. CONCLUSIONS: We revealed that TLR4 is involved in the regulation of miR-186 expression, and the anti-apoptotic effect of miR-186 on podocytes is correlated with P2×7 regulation.