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学科主题基础医学
Kindlin-2 regulates renal tubular cell plasticity by activation of Ras and its downstream signaling
Wei, Xiaofan1,2,3; Wang, Xiang1,2,3; Xia, Yang1,2,3; Tang, Yan1,2,3; Li, Feng1,2,3; Fang, Weigang1,4; Zhang, Hongquan1,2,3
关键词tubular cell plasticity kindlin-2 Ras signaling
刊名AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
2014
DOI10.1152/ajprenal.00499.2013
306期:2页:F271-F278
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Physiology ; Urology & Nephrology
研究领域[WOS]Physiology ; Urology & Nephrology
关键词[WOS]EPITHELIAL-MESENCHYMAL TRANSITION ; UNILATERAL URETERAL OBSTRUCTION ; NUCLEOTIDE EXCHANGE FACTOR ; GROWTH-FACTOR-BETA ; INTERSTITIAL FIBROSIS ; EGF RECEPTOR ; CANCER CELLS ; EMT ; MECHANISMS ; KINASE
英文摘要

Kindlin-2 is an adaptor protein that contributes to renal tubulointerstitial fibrosis (TIF). Epithelial-to-mesenchymal transition (EMT) in tubular epithelial cells was regarded as one of the key events in TIF. To determine whether kindlin-2 is involved in the EMT process, we investigated its regulation of EMT in human kidney tubular epithelial cells (TECs) and explored the underlying mechanism. In this study, we found that overexpression of kindlin-2 suppressed epithelial marker E-cadherin and increased the expression of fibronectin and the myofibroblast marker alpha-smooth muscle actin (SMA). Kindlin-2 significantly activated ERK1/2 and Akt, and inhibition of ERK1/2 or Akt reversed kindlin-2-induced EMT in human kidney TECs. Mechanistically, kindlin-2 interacted with Ras and son of sevenless (Sos)-1. Furthermore, overexpression of kindlin-2 increased Ras activation through recruiting Sos-1. Treatment with a Ras inhibitor markedly repressed kindlin-2-induced ERK1/2 and Akt activation, leading to restraint of EMT. We further demonstrated that knockdown of kindlin-2 inhibited EGF-induced Ras-Sos-1 interaction, resulting in reduction of Ras activation and suppression of EMT stimulated by EGF. Importantly, we found that depletion of kindlin-2 significantly inhibited activation of ERK1/2 and Akt signaling in mice with unilateral ureteral obstruction. We conclude that kindlin-2, through activating Ras and the downstream ERK1/2 and Akt signaling pathways, plays an important role in regulating renal tubular EMT and could be a potential therapeutic target for the treatment of fibrotic kidney diseases.

语种英语
WOS记录号WOS:000329860000014
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61714
专题北京大学基础医学院_病理学系
北京大学医学部管理机构_主任办公室党委办公室
北京大学基础医学院
作者单位1.Peking Univ, Hlth Sci Ctr, Minist Educ, Key Lab Carcinogenesis & Translat Res, Beijing 100191, Peoples R China
2.Peking Univ, Hlth Sci Ctr, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Anat Histol & Embryol, Lab Mol Cell Biol & Tumor Biol, Beijing 100191, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Dept Pathol, Beijing 100191, Peoples R China
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Wei, Xiaofan,Wang, Xiang,Xia, Yang,et al. Kindlin-2 regulates renal tubular cell plasticity by activation of Ras and its downstream signaling[J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY,2014,306(2):F271-F278.
APA Wei, Xiaofan.,Wang, Xiang.,Xia, Yang.,Tang, Yan.,Li, Feng.,...&Zhang, Hongquan.(2014).Kindlin-2 regulates renal tubular cell plasticity by activation of Ras and its downstream signaling.AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY,306(2),F271-F278.
MLA Wei, Xiaofan,et al."Kindlin-2 regulates renal tubular cell plasticity by activation of Ras and its downstream signaling".AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY 306.2(2014):F271-F278.
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