Twist Contributes to Proliferation and Epithelial-to-Mesenchymal Transition-Induced Fibrosis by Regulating YB-1 in Human Peritoneal Mesothelial Cells.

Twist Contributes to Proliferation and Epithelial-to-Mesenchymal Transition-Induced Fibrosis by Regulating YB-1 in Human Peritoneal Mesothelial Cells. Am J Pathol. 2015 Jun 5; Authors: He L, Che M, Hu J, Li S, Jia Z, Lou W, Li C, Yang J, Sun S, Wang H, Chen X Abstract Twist is overexpressed in high glucose (HG) damage of human peritoneal mesothelial cells (HPMCs) in vitro. Herein, we further identified its precise function related to fibrosis of peritoneal membranes (PMs). The overexpression and activation of Twist and YB-1 (official name, YBX1) and a transformed fibroblastic phenotype of HPMCs were found to be positively related to epithelial-mesenchymal transition progress and PM fibrosis ex vivo in 93 patients who underwent continuous ambulatory peritoneal dialysis (PD), and also in HG-induced immortal HPMCs and an animal model of PD. Evidence from chromatin immunoprecipitation and luciferase reporter assays supported that YBX1 is transcriptionally regulated by the direct binding of Twist to E-box. Overexpression of Twist and YB-1 led to an increase in epithelial-mesenchymal transition, proliferation, and cell cycle progress of HPMCs, which might contribute to PM fibrosis. In contrast, the silencing of Twist or YB-1 inhibited HG-induced growth and cell cycle progression of HPMCs; this led to a down-regulation in the expression of cyclin Ds and cyclin-dependent kinases, finally inhibiting PM fibrosis. Twist contributes to PM fibr...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research