title: BAG3 regulates ECM accumulation in renal proximal tubular cells induced by TGF-β1.
abstract: Previously we have demonstrated that Bcl-2-associated athanogene 3 (BAG3) is increased in renal fibrosis using a rat unilateral ureteral obstruction model. The current study investigated the role of BAG3 in renal fibrosis using transforming growth factor (TGF)-β1-treated human proximal tubular epithelial (HK-2) cells. An upregulation of BAG3 in vitro models was observed, which correlated with the increased synthesis of extracellular matrix (ECM) proteins and expression of tissue-type plasminogen activator inhibitor (PAI)-1. Blockade of BAG3 induction by shorting hairpin RNA suppressed the expression of ECM proteins but had no effect on PAI-1 expression induced by TGF-β1. Forced overexpression of BAG3 selectively increased collagens. TGF-β1-induced BAG3 expression in HK-2 cells was attenuated by ERK1/2 and JNK MAPK inhibitors. In addition, forced BAG3 overexpression blocked attenuation of collagens expression by ERK1/2 and JNK inhibitors. These data suggest that ERK1/2 and JNK signaling events are involved in modulating the expression of BAG3, which would ultimately contribute to renal fibrosis by enhancing the synthesis and deposition of ECM proteins.
authors.affiliation: Department of Nephrology, Shengjing Hospital, China Medical University Shenyang 110004, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Du
authors.affiliation: Department of Endocrinology & 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 & 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 & 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 & Molecular Biology, China Medical University Shenyang 110001, China.
authors.forename: Hua-Qin
authors.initials: HQ
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Shengjing Hospital, China Medical University Shenyang 110004, China.
authors.forename: Yan-Qiu
authors.initials: YQ
authors.lastname: Wang
keywords: BAG3; ECM; MAPK; tubular epithelial cell