Twist Contributes to Proliferation and Epithelial-to-Mesenchymal Transition–Induced Fibrosis by Regulating YB-1 in Human Peritoneal Mesothelial Cells
| Autor: | Lijie He, Xiangmei Chen, Jun Yang, Cuixiang Li, Jin-Ping Hu, Shiren Sun, Sutong Li, Weijuan Lou, Zhen Jia, Ming-wen Che, Hanmin Wang |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition Biology Pathology and Forensic Medicine Rats Sprague-Dawley Peritoneal Dialysis Continuous Ambulatory Fibrosis medicine Animals Humans Gene silencing Gene Silencing Epithelial–mesenchymal transition Cell Proliferation Cyclin Kinase Cell Cycle Twist-Related Protein 1 Continuous ambulatory peritoneal dialysis Epithelial Cells Peritoneal Fibrosis Cell cycle medicine.disease Rats Disease Models Animal Cancer research Y-Box-Binding Protein 1 Peritoneum Peritoneal Dialysis Chromatin immunoprecipitation |
| Zdroj: | The American Journal of Pathology. 185:2181-2193 |
| ISSN: | 0002-9440 |
| DOI: | 10.1016/j.ajpath.2015.04.008 |
| Popis: | 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 fibrosis during PD treatment, mainly through regulation of YB-1. |
| Databáze: | OpenAIRE |
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