title: Erbin inhibits TGF-β1-induced EMT in renal tubular epithelial cells through an ERK-dependent pathway.
abstract: Epithelial-to-mesenchymal transition (EMT) plays a crucial role in the progression of renal interstitial fibrosis, which finally leads to renal failure. Erbin, a member of LAP family, is recently reported to inhibit Smads and ERK pathway which are two important types of intracellular signaling involved in TGF-β1-induced EMT. However, the role of Erbin in the regulation of EMT and the underlying mechanisms remain to be fully understood. To that end, we aimed to evaluate the expression of Erbin in renal interstitial fibrosis and the potential role of Erbin in tubular EMT stimulated by TGF-β1. In this study we demonstrated that the expression of Erbin was upregulated in the tubular epithelia of 5/6-nephrectomized rats. We also showed here that TGF-β1 upregulated Erbin expression in NRK52E cells during their EMT phenotype acquisition. Importantly, elevated expression of Erbin inhibited ERK signaling and partial reversed EMT stimulated by TGF-β1. In the mean time, reducing Erbin expression enhanced ERK phosphorylation, promoted the E-cadherin suppression, and induced α-SMA expression and fibronection secretion in response to TGF-β1, which could be rescued if cells were treated with the inhibitor of MEK1/2 U0126. However, in the absence of TGF-β1, Erbin failed to affect ERK activation and EMT process. These results suggest that Erbin is a negative feedback molecule induced by TGF-β1 and inhibits TGF-β1-induced EMT via ERK signaling pathway.
authors: Division of Nephrology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Wuhan, Hubei, People's Republic of China.
authors: Qiaodan
authors: Q
authors: Zhou
authors: Rui
authors: R
authors: Zeng
authors: Chuou
authors: C
authors: Xu
authors: Lili
authors: L
authors: Liu
authors: Lin
authors: L
authors: Chen
authors: Pei
authors: P
authors: Kou
authors: Guangchang
authors: G
authors: Pei
authors: Shoujun
authors: S
authors: Bai
authors: Yamin
authors: Y
authors: Zhang
authors: Caixia
authors: C
authors: Li
authors: Song
authors: S
authors: Rong
authors: Min
authors: M
authors: Han
authors: Gang
authors: G
authors: Xu
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005355:Fibrosis; D055785:Gene Knockdown Techniques; D006801:Humans; D007677:Kidney Function Tests; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009392:Nephrectomy; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; C517630:erbin protein, rat; D020929:Mitogen-Activated Protein Kinase Kinases