title: Twist contributes to proliferation and epithelial-to-mesenchymal transition-induced fibrosis by regulating YB-1 in human peritoneal mesothelial cells.
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 fibrosis during PD treatment, mainly through regulation of YB-1.
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China; State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Lijie
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China; State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China; Department of Medicine, No. 273 Hospital of PLA, Korla, Xinjiang, People's Republic of China.
authors.forename: Mingwen
authors.initials: M
authors.lastname: Che
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China; State Key Laboratory of Cancer Biology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China; Department of Nephrology, the Central Hospital of Xi'an, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Sutong
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China; Department of Nephrology, the First Hospital of Xi'an, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Weijuan
authors.initials: W
authors.lastname: Lou
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Cuixiang
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China. Electronic address: ningsun@fmmu.edu.cn.
authors.forename: Shiren
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China. Electronic address: whm@medmail.com.cn.
authors.forename: Hanmin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Xijing Hospital, the Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China; Department of Nephrology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital and Medical College, Beijing, People's Republic of China.
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation / Q000502:physiology*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D020868:Gene Silencing; D006801:Humans; D008297:Male; D010530:Peritoneal Dialysis; D010531:Peritoneal Dialysis, Continuous Ambulatory; D056627:Peritoneal Fibrosis / Q000378:metabolism* / Q000473:pathology; D010537:Peritoneum / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D051840:Y-Box-Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051879:Twist-Related Protein 1; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human