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Programed death-ligand 1 (PD-L1, B7-H1, CD274) is a coinhibitory molecule that plays a vital role in the pathogenesis of both neoplastic and nonneoplastic diseases. However, the role of PD-L1 in primary and secondary renal diseases remains to be clarified. Previous studies have shown that both intracellular and intercellular PD-L1 participate in renal diseases via complex mechanisms. PD-L1 plays a dual role in lupus nephritis and has a protective effect in renal ischemia reperfusion injury and nephrotoxic nephritis but not in proliferative immune complex glomerulonephritis. PD-L1 supplementation, anti-PD-L1 antibodies, and D-peptide antagonists have promising application prospects in the treatment of renal diseases. In this review, we summarize the available data published on PD-L1 in renal diseases for the first time. [ABSTRACT FROM AUTHOR]

Macrophages can be alternatively activated by TGF-β1 and high-ambient glucose, in which the role of Smad2 and the crosstalk between ERK and Smad2 pathways are not fully understood. The activation of ERK and Smad2 pathways and the expression of arginase-1 were detected by Western blot. The role of Smad2 and the relationship between ERK and Smad2 pathways were investigated by using biochemical inhibitors. The protein of arginase-1 was significantly overexpressed in RAW264.7 cells stimulated by TGF-β1 and high-ambient glucose, which can be partially blocked by not only U0126 (ERK inhibitor) but also SB431542 (Smad2 inhibitor). Furthermore, simply inhibiting one pathway had no effect on the other pathway. In conclusion, both ERK and Smad2 signal pathways are involved in the activation of macrophages induced by TGF-β1 and high-ambient glucose, while there is no crosstalk shown in the process. [ABSTRACT FROM PUBLISHER]

Macrophage can be alternatively activated by TGF-β1, whether high-ambient glucose can enhance the sensitivity of TGF-β1 and the intracellular mechanisms involved in this process are not fully understood. We examined whether the mitogen-activated protein kinase is involved in the activation of macrophage induced by TGF-β1 and high-ambient glucose. The expression of arginase-1, CD206 and TGF-β1 was accessed by Western blot and immunofluorescence in RAW 264.7 cells stimulated with TGF-β1 and high-ambient glucose. The activation of MAPK pathways in the process was investigated by Western blot. The role of MAPK was assessed using biochemical inhibitors. The protein of arginase-1, CD206 and TGF-β1 was significantly overexpressed in RAW264.7 cells stimulated by TGF-β1 and high-ambient glucose. ERK and JNK phosphorylation occurred in 30 min and p38MAPK phosphorylation occurred in 30 min and 24 h after the stimulation. And the expression of arginase-1 and TGF-β1 was partially blocked by the pretreated ERK biochemical inhibitor (U0126) instead of the JNK inhibitor (SP600125) and p38MAPK inhibitor (SB203580). In conclusion, high-ambient glucose can enhance the sensitivity of TGF-β1 in RAW264.7 cells, which resulted in overexpression of TGF-β1 and arginase-1 in macrophages. ERK plays a role in this process. [ABSTRACT FROM PUBLISHER]

Association between endothelial nitric oxide synthase (eNOS) gene polymorphism and Henoch-Schönlein purpura (HSP)/Henoch-Schönlein purpura nephritis (HSPN) risk is still controversial. A meta-analysis was performed to evaluate the association between eNOS gene polymorphism and HSP/HSPN susceptibility. A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic database. Three articles were identified for the analysis of association between eNOS gene polymorphism and HSPN/HSP risk. eNOS G894T gene polymorphism was not associated with HSPN susceptibility and the risk of patients with HSP developing into HSPN. Interestingly, eNOS G894T T allele and GG genotype were associated with HSP susceptibility, but not the TT genotype. eNOS T786C TT genotype was associated with HSPN susceptibility, but not C allele and CC genotype. Furthermore, eNOS T786C gene polymorphism was not associated with HSP risk and the risk of patients with HSP developing into HSPN. In conclusion, eNOS T786C TT genotype was associated with and eNOS G894T T allele and GG genotype were associated with HSP susceptibility. However, more studies should be performed in the future. [ABSTRACT FROM AUTHOR]

The relationship between peroxisome proliferator-activated receptor gamma ( PPARγ) Pro12Ala gene polymorphism and type 2 diabetic nephropathy (T2DN) risk in Asians is still unclear. This study was performed to evaluate if there was an association between the PPARγ Pro12Ala gene polymorphism and T2DN risk in Asians using meta-analysis. The relevant reports were searched and identified from PubMed, Cochrane Library and CBM-disc (China Biological Medicine Database) on 1 October 2013, and eligible studies were included and synthesized. Ten reports were recruited into this meta-analysis for the association of the PPARγ Pro12Ala gene polymorphism with T2DN risk. The Pro12Ala gene polymorphism in the Asian population was shown to be not associated with T2DN risk (Ala/Ala: OR = 0.67, 95% CI: 0.22-2.00, p = 0.47; Pro/Pro: OR = 1.77, 95% CI: 0.82-1.65, p = 0.39; Ala allele: OR = 0.74, 95% CI: 0.47-1.16, p = 0.19). In the sensitivity analysis according to Hardy-Weinberg equilibrium (HWE), the control source from hospital, the control source from population, the genotyping methods using PCR-RFLP, the genotyping methods using Taqman, sample size of case (≥100), the association of the PPARγ Pro12Ala gene polymorphism with T2DN risk was also not found. Interestingly, in the sensitivity analysis according to sample size of case (<100), Ala allele was associated with T2DN risk, but not the Pro/Pro genotype. However, the sample size for sensitivity analysis according to sample size of case (<100) was relatively small and therefore, the results should be interpreted with care. In conclusion, the PPARγ Pro12Ala gene polymorphism was not associated with T2DN risk in Asians. However, Ala allele was associated with T2DN risk when the sample size of case was less than 100. Nonetheless, additional studies are required to firmly establish a correlation between the PPARγ Pro12Ala gene polymorphism and T2DN risk in Asians. [ABSTRACT FROM AUTHOR]

Serum fetuin A has been shown to be associated with the risk of vascular calcification and atherosclerosis, and it can predict the onset of cardiovascular mortality in dialysis patients. The carotid intima-media thickness (cIMT) is an accessible and reliable method to identify the subclinical atherosclerosis. The aim of this study was to investigate the relationships between dialysate calcium concentrations and fetuin A or cIMT in patients undergoing peritoneal dialysis (PD). Forty patients, newly diagnosed end-stage renal disease (ESRD) and undergoing peritoneal dialysis, were enrolled in the study, with a calcium content of the peritoneal dialysis (PD) solution of 1.25 mmol/L in 20 patients (low-Ca group) and 1.75 mmol/L in 20 patients (standard-Ca group). The patients were followed up for 12 months after the PD conducted. Serum fetuin A was determined using a human fetuin A enzyme-linked immunosorbent assay kit and cIMT was detected using ultrasonic wave. We observed no difference between two groups with regard to the baseline data of fetuin A, cIMT, calcium, phosphorus, calcium-phosphorus product, high sensitivity CRP (hsCRP), parathyroid hormone (PTH), or lipid parameters. After 12 months follow-up, fetuin A (263.92 ± 16.1 vs. 282.76 ± 21.0, p = 0.017) and calcium-phosphorus product (39.85 ± 7.76 vs. 47.50 ± 6.65, p = 0.009) were obviously lower in the low-Ca group than standard-Ca group, the other serum parameters were not different between these two groups. Compared with baseline data, serum fetuin A concentration significantly reduced in low-Ca group ( p < 0.05). The number of patients with increased cIMT and newly occurring cardiovascular events in the low-Ca group were significantly reduced than standard-Ca group ( p < 0.05). In conclusion, our data suggest that low calcium dialysate treatment is associated with the decreased serum fetuin A concentration and serum calcium-phosphorus product, and it is associated with the reduced number of PD patients with increased cIMT or with newly occurring cardiovascular events. However, more studies with lager sample size should be performed in the future. [ABSTRACT FROM AUTHOR]