Silencing of lncRNA 6030408B16RIK prevents ultrafiltration failure in peritoneal dialysis via microRNA-326-3p-mediated WISP2 down-regulation

Abstract

Continuous exposure to peritoneal dialysis (PD) fluid results in peritoneal fibrosis and ultimately causes ultrafiltration failure. Noncoding RNAs, including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), have been reported to participate in ultrafiltration failure in PD. Therefore, our study aimed to investigate the mechanism of lncRNA 6030408B16RIK in association with miR-326-3p in ultrafiltration failure in PD. Peritoneal tissues were collected from uremic patients with or without PD. A uremic rat model with PD was first established by 5/6 nephrectomy. The relationship between lncRNA 6030408B16RIK, miR-326-3p and WISP2 was identified using luciferase reporter, RNA pull-down and RIP assays. After ectopic expression and depletion treatments in cells, expression of α-SMA, phosphorylated β-catenin, FSP1, E-cadherin and Vimentin was evaluated by RT-qPCR and Western blot analyses, and Collagen III and CD31 expression by immunohistochemistry. Ultrafiltration volume and glucose transport capacity were assessed by the peritoneal equilibration test. Expression of lncRNA 6030408B16RIK and WISP2 was up-regulated and miR-326-3p expression was poor in peritoneal tissues of uremic PD patients and model rats. LncRNA 6030408B16RIK competitively bound to miR-326-3p and then elevated WISP2 expression. Silencing of lncRNA 6030408B16RIK and WISP2 or overexpression of miR-326-3p was shown to decrease the expression of α-SMA, phosphorylated β-catenin, FSP1, Vimentin, Collagen III and CD31, while reducing glucose transport capacity and increasing E-cadherin expression and ultrafiltration volume in uremic PD rats. In summary, lncRNA 6030408B16RIK silencing exerts an anti-fibrotic effect on uremic PD rats with ultrafiltration failure by inactivating the WISP2-dependent Wnt/β-catenin pathway via miR-326-3p.

A genome-wide association study suggests correlations of common genetic variants with peritoneal solute transfer rates in patients with kidney failure receiving peritoneal dialysis

“…50 Cell culture or animal studies have identified lncRNAs such as AV310809 as promoters or AK089579 and 6030408B1RIK as inhibitors of EMT of peritoneal mesothelial cells. [51][52][53] In conjunction with these prior studies, our findings underscore the potential importance of lncRNAs in peritoneal biology and pathobiology.…”

LncRNA GAS5 Competitively Combined With miR-21 Regulates PTEN and Influences EMT of Peritoneal Mesothelial Cells via Wnt/β-Catenin Signaling Pathway

“…The latest research suggests that lncRNAs have a specific expression profile in fibrotic tissues such as lung, kidney, liver, heart, and peritoneum ( Cao et al, 2013 ; Liu et al, 2015 ). Several researchers revealed that lncRNA-AV310809, 6030408B16RIK, and AK089579 modulate peritoneal EMT ( Wei et al, 2019 ; Zhang et al, 2019 ; Wang Z. et al, 2020 ). However, the specific role and related mechanisms of lncRNA in peritoneal fibrosis remain unclear.…”

Blocking core fucosylation of epidermal growth factor (EGF) receptor prevents peritoneal fibrosis progression

“…Peritoneal dialysis (PD), a type of home dialysis therapy for end-stage renal disease, has been widely used across the world because of its convenience and flexibility [ 1 ], especially in the current COVID-19 pandemic [ 2 ]. However, long-term PD treatment will result in peritoneal fibrosis, a frequent complication due to exposure to glucose peritoneal dialysate [ 3 , 4 ]. Peritoneal fibrosis may affect the function of the peritoneal membrane and ultimately lead to ultrafiltration failure and discontinuation of PD [ 5 , 6 ].…”