title: AEG-1 participates in TGF-beta1-induced EMT through p38 MAPK activation.
abstract: Epithelial-mesenchymal transition (EMT) is an important cellular event in organogenesis, cancer and renal tubulointerstitial fibrosis. Transforming growth factor-beta1 (TGF-beta1) is the key inducer of EMT and the p38 mitogen-activated protein kinases (p38 MAPK), an major intracellular signal transduction pathway is involved in TGF-beta1-induced EMT. Astrocyte elevated gene-1 (AEG-1) represents an chief genetic determinant regulating multiple events in tumorigenesis. Our present study is to explore the role of AEG-1 in TGF-beta1-induced p38 MAPK activation and EMT process in human renal tubular epithelial (HK-2) cells. The protein expressions of AEG-1, the markers of EMT and p38 phosphorylation were measured by Western blot. The protein expression of AEG-1 was increased in HK-2 cells treated with TGF-beta1. Knockdown of AEG-1 potently inhibited phosphorylation of p38 MAPK and reversed TGF-beta1-induced EMT. Over-expression of AEG-1 via AEG-1 transfection elicited p38 MAPK phosphorylation and promoted EMT. The effects of AEG-1 during EMT were blocked by a p38-specific inhibitor. Our findings suggest that AEG-1 plays an important role in TGF-beta1-induced EMT through activation of p38 MAPK in proximal tubular epithelial cells.
authors: Department of Nephrology, Hainan General Hospital, Haikou, Hainan 570311, China.
authors: Jiali
authors: J
authors: Wei
authors: Zhuori
authors: Z
authors: Li
authors: Wenfang
authors: W
authors: Chen
authors: Chunyang
authors: C
authors: Ma
authors: Feng
authors: F
authors: Zhan
authors: Wei
authors: W
authors: Wu
authors: Youming
authors: Y
authors: Peng
mesh_terms: D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008565:Membrane Proteins; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases
keywords: astrocyte elevated gene-1; epithelial-mesenchymal transition; p38 mitogen-activated protein kinases; renal tubulointerstitial fibrosis; transforming growth factor-beta1