Abnormal lncRNA CCAT1/microRNA-155/SIRT1 axis promoted inflammatory response and apoptosis of tubular epithelial cells in LPS caused acute kidney injury.

BACKGROUNDS: Acute kidney injury (AKI) is characterized by excessive inflammatory response and apoptosis in tubular epithelial cells. Recent studies suggested that long non-coding RNAs colon cancer-associated transcript-1 (CCAT-1) and microRNA-155 (miR-155) might regulate cell death and inflammation. We aimed to explore the role of CCAT-1/miRNA-155 axis in the AKI. METHODS: LPS was applied to establish in vitro and in vivo models of AKI using HK2 cells and pcDNA-CCAT1 transgenic mice, respectively. Gene overexpression or knockdown were performed through plasmids transfection. Apoptosis were determined by qRT-PCR, western blotting (Fas, FasL, Caspase-3), AnnexinV/PI staining and TUNEL assay. Cytokines were assessed by ELISA. Interaction of CCAT1/miR-155 and miR-155/SIRT1 were detected by dual-luciferase reporter assay. RNA immunoprecipitation (RIP) was also performed to determine CCAT1/miR-155 interaction. Pathological changes of AKI were evaluated using H&E staining, blood urine nitrogen (BUN) and serum creatinine (Cr) detection kits. The degree of renal fibrosis was determined by Masson trichrome stain. RESULTS: LPS administration reduced CCAT1 and SIRT1 expression, but increased miR-155 levels in tubular epithelial cells in vitro. Luciferase assay demonstrated that miR-155 might bind to and regulate CCAT1 and SIRT1. RIP further confirmed the direct interaction of CCAT1 and miR-155. Restoration of CCAT1 attenuated LPS induced inflammation and apoptosis through sequestering miR-155. The anti-inflammation and pro-survival effects of CCAT1 overexpression and miR-155 inhibition were abolished by SIRT1 knockdown, as indicated by the expression of cytokine and apoptotic markers, as well as H&E, BUN and Cr detection. Dysregulated CCAT1/miR-155/SIRT1 pathway regulated disease progression in a murine model of LPS-induced AKI, and NF-κB pathway involved in. CONCLUSION: CCAT1 restoration sequestered miR-155, leading to upregulation of SIRT1 and alleviated LPS induced renal tubular epithelial cell damage in vitro and in vivo.

Diagnostic significance of PLA2R and IgG4 in elderly patients with idiopathic membranous nephropathy / 解放军医学杂志

Objective To evaluate the diagnostic significance of PLA2R and IgG4 in elderly patients with idiopathic membranous nephropathy (IMN).Methods The clinical data were retrospectively analyzed of patients with IMN (49 males and 49 females,aged 66.6 ± 5.4 years) or Non-IMN (57 males and 41 females,aged 67.1 ± 6.5 years) who were admitted in the authors served Department of Nephrology from Apr.2014 to Feb.2016 and accepted renal biopsy.SPSS13.0 was employed to evaluate the sensitivity,specificity and calculate the area under ROC curve (AUC) of serum anti-PLA2R antibody,glomerular PLA2R and IgG1-4 subclasses on diagnosing IMN.Results On diagnosing IMN,the sensitivity and specificity of serum anti-PLA2R antibody were 77.6％ and 89.8％ [AUC=0.869(0.816-0.923)],of glomerular PLA2R were 66.3％ and 94.9％ [AUC=0.805(0.741-0.87)],and of glomerular IgGl-IgG4 were 80.6％ and 78.6％,60.2％ and 83.7％,41.8％ and 84.7％,and 93.9％ and 89.8％,respectively [AUC=0.767(0.696-0.838),0.709(0.635-0.783),0.628(0.549-0.706) and 0.94(0.901-0.978),respectively].As to the combined use of glomerular PLA2R and IgG4 on diagnosing IMN,the sensitivity was 93.9％ when either one of glomerular PLA2R and IgG4 was positive,or the specificity was 96.9％ when both glomerular PLA2R and IgG4 were positive.Conclusion PLA2R and IgG4 can effectively serve the diagnosis of IMN,and the combined use of PLA2R and IgG4 may be better than single indicator alone.

Effect of WNT5A on epithelial-mesenchymal transition and its correlation with tumor invasion and metastasis in nasopharyngeal carcinoma

OBJECTIVE@#To investigate the correlation between nasopharyngeal carcinoma cell WNT5A and epithelial-mesenchymal transition (emt)/metastasis, and investigate its possible mechanisms.@*METHODS@#RT-PCR and gene transfection were used to detect the expression of nasopharyngeal carcinoma cell strains WNT5A and EMT related factor 5-8F. Transient transfection of NPC cell line 5-8F was determined by liposome of plasmid with WNT5A gene. The differential expressions of WNT5A and EMT-related factors in cells before and after transfection were detected by RT-PCR. Cell scratch assay and Transwell assay were used to detect the motility abilities of cells before and after 5-8F transfection.@*RESULTS@#The expressions of WNT5A and EMT related factors matrix metalloproteinase-2 of the WNT5A transferred group in the nasopharyngeal carcinoma cell line 5-8F were higher than the blank control group and the empty vector transferred group, and the transfer ability of the WNT5A transferred group was higher than that in the blank control group and the empty vector transferred group, while the expressions of EMT related factors E-cadherin were lower than that in the blank control group and the empty vector transferred group, and the transfer ability of the WNT5A transferred group was higher than that in the blank control group and the empty vector transferred group.@*CONCLUSIONS@#In nasopharyngeal carcinoma cells, WNT5A can regulate the epithelial-mesenchymal transition and affect the ability of tumor invasion and metastasis of nasopharyngeal carcinoma.

Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats

OBJECTIVE@#To investigate the effect of acute renal ischemia reperfusion on brain tissue.@*METHODS@#Fourty eight rats were randomly divided into four groups (n=12): sham operation group, 30 min ischemia 60 min reperfusion group, 60 min ischemia 60 min reperfusion group, and 120 min ischemia 60 min reperfusion group. The brain tissues were taken after the experiment. TUNEL assay was used to detect the brain cell apoptosis, and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.@*RESULTS@#Renal ischemia-reperfusion induced apoptosis of brain tissues, and the apoptosis increased with prolongation of ischemia time. The detection at the molecular level showed decreased Bcl-2 expression, increased Bax expression, upregulated expression of NF-κB and its downstream factor COX-2/PGE2.@*CONCLUSIONS@#Acute renal ischemia-reperfusion can cause brain tissue damage, manifested as induced brain tissues apoptosis and inflammation activation.

Association between dyslipidemia and chronic kidney disease: a cross-sectional study in the middle-aged and elderly Chinese population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Dyslipidemia, a well-known risk factor for cardiovascular disease, is common in patients with kidney disease. Recent studies discerned that dyslipidemias play a critical role in renal damage progression in renal diseases, but the association between dyslipidemias and chronic kidney disease (CKD) in the general population remains unknown. Thus, we assessed whether the growing prevalence of dyslipidemia could increase the risk of CKD.</p><p><b>METHODS</b>A total of 4779 middle-aged and elderly participants participated in this study. Dyslipidemias were defined by the 2007 Guidelines in Chinese Adults. Incident CKD was defined as albuminuria and/or reduced estimated glomerular filtration rate (eGFR, < 60 ml×min(-1)×1.73 m(-2)). Regression analysis was used to evaluate the association between dyslipidemia and albuminuria/reduced eGFR.</p><p><b>RESULTS</b>Participants with hypercholesterolemia exhibited a greater prevalence of albuminuria and reduced eGFR (10.0% vs. 6.1%, P = 0.001; 4.0% vs. 2.4%, P = 0.028, respectively). Both hypercholesterolemia and low high density lipoprotein cholesterol (HDL-C) were independently associated with albuminuria (odds ratio (OR) 1.49; 95% confidence interval (CI) 1.08 - 2.07 and OR 1.53; 95%CI 1.13 - 2.09, respectively). The multivariable adjusted OR of reduced eGFR in participants with hypercholesterolemia was 1.65 (95%CI 1.03 - 2.65). As the number of dyslipidemia components increased, so did the OR of CKD: 0.87 (95%CI 0.65 - 1.15), 1.29 (95%CI, 0.83 - 2.01), and 7.87 (95%CI, 3.75 - 16.50) for albuminuria, and 0.38 (95%CI 0.21 - 0.69), 1.92 (95%CI 1.14 - 3.25), and 5.85 (95%CI 2.36 - 14.51) for reduced eGFR, respectively.</p><p><b>CONCLUSIONS</b>Our findings indicate that dyslipidemias increase the risk of CKD in the middle-aged and elderly Chinese population. Hypercholesterolemia plays an important role in reducing total eGFR. Both low HDL-C and hypercholesterolemia are associated with an increased risk for albuminuria.</p>