Biochemical and Biophysical Research Communications, Vol.513, No.1, 119-126, 2019
Novel long non-coding RNA AV310809 promotes TGF-beta 1 induced epithelial-mesenchymal transition of human peritoneal mesothelial cells via activation of the Wnt2/beta-catenin signaling pathway
Peritoneal fibrosis (PF) is a crucial cause of the loss of peritoneal function in patients with peritoneal dialysis. To better understand the underlying mechanism of PF, we selected AV310809, which is one of the most highly upregulated IncRNA in fibrotic peritoneal tissue, for functional analysis. We used co-expression analysis to explore the potential relationship between AV310809 and coding genes. qPCR, WB and IF were applied to evaluate the expression and localization of AV310809, epithelial markers and proteins involved in the Wnt2/beta-catenin signaling pathway. The interaction between AV310809 and beta-catenin was examined using an RNA pulldown assay. The expression level of AV310809 was upregulated in fibrotic peritoneum and TGF-beta 1 induced EMT in HPMCs. Ectopic overexpression of AV310809 promoted EMT and activated the Wnt2/beta-catenin signaling pathway. Furthermore, we demonstrated that AV310809 could interact with beta-catenin and blocking beta-catenin inhibited the augmentation of EMT by AV310809. These findings indicated that AV310809 promoted TGF-beta 1 induced EMT in HPMCs through the activation of the Wnt2/beta-catenin signaling pathway, possibly by targeting beta-catenin. We suggest that AV310809 may be a new therapeutic target for the management of peritoneal dialysis-associated PF. (C) 2019 The Authors. Published by Elsevier Inc.
Keywords:Long non-coding RNA;Epithelial-mesenchymal transition;Peritoneal fibrosis;Wnt2/beta-catenin signaling pathway