title: Implication of Bcl-2-associated athanogene 3 in fibroblast growth factor-2-mediated epithelial-mesenchymal transition in renal epithelial cells.
abstract: The epithelial-mesenchymal transition (EMT) of tubular epithelial cells to myofibroblast-like cells plays a substantial role in renal tubulointerstitial fibrosis, which is a common pathological character of end-stage renal disease (ESRD). Fibroblast growth factor-2 (FGF-2) triggers EMT in tubular epithelial cells and increases Bcl-2-associated athanogene 3 (BAG3) expression in neural progenitor and neuroblastoma cells. In addition, a novel role of regulation of EMT has been ascribed to BAG3 recently. These previous reports urged us to study the potential involvement of BAG3 in EMT triggered by FGF-2 in renal tubular epithelial cells. The current study found that FGF-2 induced EMT, simultaneously increased BAG3 expression in human kidney 2 (HK2) cells. Although FGF-2 induced EMT in nontransfected or scramble short hairpin RNA (shRNA) transfected HK2 cells, it was ineffective in BAG3-silenced cells, indicating a favorable role of BAG3 in EMT of tubular cells induced by FGF-2. Knockdown of BAG3 also significantly suppressed motion and invasion of HK2 cells mediated by FGF-2. Furthermore, we confirmed that BAG3 was upregulated in kidney of unilateral ureteral obstruction (UUO) rats, a well-established renal fibrosis model, in which EMT is supposed to exert a substantial influence on renal fibrosis. Importantly, upregulation of BAG3 was limited to tubular epithelial cells. Results of the current study identify BAG3 as a potential player in EMT of tubular epithelial cells, as well as renal fibrosis.
authors.affiliation: Department of Nephrology, Shengjing Hospital, China Medical University, Shenyang 110004, China dolphine_doctor@hotmail.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Du
authors.affiliation: Department of Endocrinology and Metabolism, the 1st Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Si
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, the 1st Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Geriatrics, the 1st Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Shengjing Hospital, China Medical University, Shenyang 110004, China.
authors.forename: De-Tian
authors.initials: DT
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, the 1st Affiliated Hospital, China Medical University, Shenyang 110001, China.
authors.forename: Zhen-Xian
authors.initials: ZX
authors.lastname: Du
authors.affiliation: Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001, China.
authors.forename: Hua-Qin
authors.initials: HQ
authors.lastname: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000166:cytology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C414431:BAG3 protein, human; D015415:Biomarkers; D016222:Fibroblast Growth Factor 2
keywords: BAG3; EMT; FGF-2; tubular epithelial cell