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ETS2 promotes epithelial-to-mesenchymal transition in renal fibrosis by targeting JUNB transcription.
Yao, Fang; Wang, Xiaojing; Cui, Zhong-Kai; Lan, Haibing; Ai, Xiaolan; Song, Qiancheng; Chen, Zhenguo; Yang, Jun; Wu, Bingyi; Bai, Xiaochun.
Afiliação
  • Yao F; Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • Wang X; Research Center of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
  • Cui ZK; Research Center of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
  • Lan H; Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • Ai X; Department of the Intensive Care Unit, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China.
  • Song Q; Research Center of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
  • Chen Z; Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • Yang J; Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • Wu B; Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
  • Bai X; Research Center of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. wubingyi66@126.com.
Lab Invest ; 100(3): 438-453, 2020 03.
Article em En | MEDLINE | ID: mdl-31641227
ABSTRACT
Epithelial-to-mesenchymal transition (EMT) plays an important role in the progression of renal tubulointerstitial fibrosis, a common mechanism leading to end-stage renal failure. V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2), a transcription factor, exhibits diverse roles in pathogenesis; however, its role in renal fibrosis is not yet fully understood. In this study, we detected the expression of ETS2 in an animal model of renal fibrosis and evaluated the potential role of ETS2 in tubular EMT induced by TGF-ß1. We found that ETS2 and profibrogenic factors, alpha-smooth muscle actin (α-SMA) and fibronectin (FN), were significantly increased in the unilateral ureteral obstruction (UUO)-induced renal fibrosis model in mice. In vitro, TGF-ß1 induced a high expression of ETS2 dependent on Smad3 and ERK signaling pathway in human proximal tubular epithelial cells (HK2). Knockdown of ETS2 abrogated TGF-ß1-mediated expression of profibrogenic factors vimentin, α-SMA, collagen I, and FN in HK2 cells. Mechanistically, ETS2 promoted JUNB expression in HK2 cells after TGF-ß1 stimulation. Furthermore, luciferase and Chromatin Immunoprecipitation (ChIP) assays revealed that the binding of ETS2 to three EBS motifs on the promoter of JUNB triggered its transcription. Notably, silencing JUNB reversed the ETS2-induced upregulation of the profibrogenic factors in HK2 cells after TGF-ß1 stimulation. These findings suggest that ETS2 mediates TGF-ß1-induced EMT in renal tubular cells through JUNB, a novel pathway for preventing renal fibrosis.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Fibrose / Proteína Proto-Oncogênica c-ets-2 / Transição Epitelial-Mesenquimal / Nefropatias Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Fibrose / Proteína Proto-Oncogênica c-ets-2 / Transição Epitelial-Mesenquimal / Nefropatias Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2020 Tipo de documento: Article