LncRNA ANRIL-mediated miR-181b-5p/S1PR1 axis is involved in the progression of uremic cardiomyopathy through activating T cells.

This study aimed to explore the regulatory role of lncRNA ANRIL/miR-181b-5p/S1PR1 in UC. UC mouse model was established by 5/6th nephrectomy. We detected body weight, serum levels of renal function and inflammatory factors (biochemical analyzer/ELISA), and cardiac parameters (echocardiography). HE and Masson staining showed the pathological changes and fibrosis in myocardial and nephridial tissues. The expression of ANRIL, miR-181b-5p, and S1PR1 were detected by qRT-PCR or Western blot/immunofluorescence. T cells activation was analyzed by Flow cytometry. ANRIL/S1PR1 were up-regulated and miR-181b-5p was down-regulated in UC mice. ANRIL silencing up-regulated miR-181b-5p and down-regulated S1PR1 (a target of miR-181b-5p). ANRIL silencing increased the body weight, recovered renal function [decreased blood urea nitrogen (BUN) and serum creatinine (Scr)] and cardiac function [decreased left ventricular end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), LV systolic anterior wall thickness (LVAWS), LV end-diastolic anterior wall thickness (LVAWD), myocardial performance index (MPI), and isovolumic relaxation time (IVRT); increased LV ejection fraction (LVEF), LVEF/MPI, fractional shortening (FS), and E- and A-waves (E/A)], inhibited the inflammation [decreased interferon (IFN)-γ, interleukin (IL)-2, IL-10, and tumor necrosis factor (TNF)-α], and relieved pathological injuries and fibrosis. ANRIL silencing also recovered the viability and inhibited the inflammation of activated T cells in vitro, and inhibited T cell activation in UC mice in vivo. In addition, miR-181b-5p overexpression exhibited same effects with ANRIL silencing in UC. ANRIL silencing inhibited T cell activation through regulating miR-181b-5p/S1PR1, contributing to the remission of UC.

The association between socioeconomic status and prevalence of chronic kidney disease: A cross-sectional study among rural residents in eastern China.

To investigate the prevalence of chronic kidney disease (CKD) among eastern Chinese rural residents and analyze the relationship between socioeconomic conditions and CKD.A cross-sectional survey of 1713 adults, enrolled from 4 villages in the north-central part of Zhejiang province in eastern China was conducted by collecting data on socioeconomic status, physical examination, and laboratory investigations. CKD was defined as estimated glomerular filtration rate < 60 mL/min per 1.73 m or urinary albumin/creatinine ratio more than 30 mg/g. The crude and adjusted prevalence of CKD was estimated and the association of socioeconomic status was analyzed by logistic regression.A total of 1654 adults (96.53%) completed the screening, and 1627 (98.37%) of them had complete questionnaire and test information. The standardized prevalence of CKD adjusted by age and sex was 9.21% (95% confidence interval, 7.8-10.63). People with hypertension, hyperglycemia, hyperuricemia, high fasting blood glucose, and high body mass index had higher risk for CKD. Socioeconomic status was found to be partly related to CKD, especially educational level and occupational nature.A high prevalence of CKD was observed among rural residents in north-central Zhejiang province in eastern China. Socioeconomic statuses were partly related to the prevalence of CKD.

Tamoxifen attenuates dialysate-induced peritoneal fibrosis by inhibiting GSK-3ß/ß-catenin axis activation.

Peritoneal fibrosis is a severe complication arising from long-term peritoneal dialysis (PD). Tamoxifen (Tamo) has been clinically proven effective in a series of fibrotic diseases, such as PD-associated encapsulating peritoneal sclerosis (EPS), but the mechanisms underlying Tamoxifen's protective effects are yet to be defined. In the present study, C57BL/6 mice received intraperitoneal injections of either saline, 4.25% high glucose (HG) PD fluid (PDF) or PDF plus Tamoxifen each day for 30 days. Tamoxifen attenuated thickening of the peritoneum, and reversed PDF-induced peritoneal expression of E-cadherin, Vimentin, matrix metalloproteinase 9 (MMP9), Snail, and ß-catenin. Mouse peritoneal mesothelial cells (mPMCs) were cultured in 4.25% glucose or 4.25% glucose plus Tamoxifen for 48 h. Tamoxifen inhibited epithelial-to-mesenchymal transition (EMT) as well as phosphorylation of glycogen synthase kinase-3ß (GSK-3ß), nuclear ß-catenin, and Snail induced by exposure to HG. TWS119 reversed the effects of Tamoxifen on ß-catenin and Snail expression. In conclusion, Tamoxifen significantly attenuated EMT during peritoneal epithelial fibrosis, in part by inhibiting GSK-3ß/ß-catenin activation.

Beta-catenin participates in dialysate-induced peritoneal fibrosis via enhanced peritoneal cell epithelial-to-mesenchymal transition.

Long-term exposure to peritoneal dialysate with high glucose (HG) leads to peritoneal fibrosis and thus decreases dialysis efficiency. In this study, we explored the role of ß-catenin in this process. C57BL/6 mice received daily intraperitoneal injection with 10% of the body weight of saline (control), 4.25% glucose peritoneal dialysis fluid (PDF), or PDF combined with 5 mg·kg-1 of the ß-catenin inhibitor ICG-001 (PDF+ICG) for 30 days. Also, mice peritoneal epithelial cells (mPECs) were cultured in 4.25% glucose (HG) or combined with 10 µm ICG-001 (HG+ICG) for 48 h. We found greater thickness of the parietal peritoneum in the PDF-treated mice. Additionally, lower expression of E-cadherin, higher expression of Vimentin, ß-catenin, and Snail, and activation of ß-catenin was observed in the mice and in HG-treated mPECs, all of which were reversed by ICG-001. The changes in E-cadherin and Vimentin indicated occurrence of the epithelial-to-mesenchymal transition (EMT). Thus, ß-catenin signaling participates in the process of HG-induced peritoneal fibrosis, and the EMT of peritoneal epithelial cells is one of the underlying mechanisms of this pathological change.