GSK3β attenuates TGF-β1 induced epithelial-mesenchymal transition and metabolic alterations in ARPE-19 cells

被引：17
作者：
Huang, Li [1 ]
Zhang, Cheng [1 ]
Su, Li [1 ]
Song, Zhengyu [1 ,2 ]
机构：
[1] Shanghai Jiao Tong Univ, Sch Med, Dept Ophthalmol, Shanghai Gen Hosp, Shanghai 200080, Peoples R China
[2] Shanghai Xinshijie Eye Hosp, Shanghai 200071, Peoples R China
来源：
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2017年 / 486卷 / 03期
基金：
中国国家自然科学基金;
关键词：
Glycogen synthase kinase 3 beta; Transforming growth factor-beta; Epithelial-mesenchymal transition; Metabolomics; ARPE-19; cells; PROLIFERATIVE VITREORETINOPATHY; OXIDATIVE STRESS; PROMOTES; DISEASE;
D O I：
10.1016/j.bbrc.2017.03.113
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
While TGF-beta 1 is known to induce epithelial mesenchymal transition (EMT), a major factor in the pathogenesis of proliferative vitreoretinopathy (PVR), in ARPE-19 cells. The molecular pathways involved in EMT formation have not yet to be fully characterized. In this study, we have found that TGF-beta 1-mediated induction of EMT in ARPE-19 cells varied in a dose- and time-dependent manner. Specifically, TGF-beta 1 inhibited GSK-beta 3 by accelerating phosphorylation at ser9. GSK-3 beta inhibitor or knockdown of GSK-beta 3 resulted in enhanced TGF-beta 1-mediated EMT, migration and collagen contraction in ARPE-19 cells, which were then abrogated by GSK-beta 3 overexpression and PI3K/AKT inhibitor. Importantly, GSK-beta 3 also mediated metabolic reprogramming in TGF-beta 1-treated cells. Our results indicate that GSK-3 beta plays a pivotal role in TGF-beta 1-mediated EMT in ARPE-19 cells. (C) 2017 Elsevier Inc. All rights reserved.
引用
收藏
页码：744 / 751
页数：8
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