HSP47 regulates ECM accumulation in renal proximal tubular cells induced by TGF-β1 through ERK1/2 and JNK MAPK pathways

被引:68
作者
Xiao, Hong-bo [1 ,3 ]
Liu, Rui-hong [2 ]
Ling, Guang-hui [1 ]
Xiao, Li [1 ]
Xia, Yuan-chen [1 ]
Liu, Fu-you [1 ]
Li, Jun [1 ]
Liu, Ying-hong [1 ]
Chen, Qin-kai [3 ]
Lv, Jin-lei [3 ]
Zhan, Ming [1 ]
Yang, Shi-kun [1 ]
Kanwar, Yashpal S. [4 ,5 ]
Sun, Lin [1 ]
机构
[1] Cent S Univ, Kidney Inst, Xiangya Hosp 2, Dept Nephrol, Changsha 410011, Hunan, Peoples R China
[2] Cent S Univ, Kidney Inst, Xiangya Hosp 2, Dept Geriatr, Changsha 410011, Hunan, Peoples R China
[3] Nan Chang Univ, Affiliated Hosp 1, Dept Nephrol, Nanchang, Jiangxi, Peoples R China
[4] Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA
[5] Northwestern Univ, Dept Med, Chicago, IL 60611 USA
关键词
heat shock protein 47; transforming growth factor-beta(1); renal proximal tubular cell; fibrosis; extracellular signal-regulated protein kinase 1/2; c-Jun NH2-terminal kinase; mitogen-activated protein kinase; SHOCK-PROTEIN; 47; TUBULOINTERSTITIAL FIBROSIS; TRANSCRIPTIONAL ACTIVATION; UP-REGULATION; TGF-BETA; EXPRESSION; KINASE; HEAT-SHOCK-PROTEIN-47; NEPHROPATHY; SUPPRESSION;
D O I
10.1152/ajprenal.00470.2011
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Xiao H, Liu R, Ling G, Xiao L, Xia Y, Liu F, Li J, Liu Y, Chen Q, Lv J, Zhan M, Yang S, Kanwar YS, Sun L. HSP47 regulates ECM accumulation in renal proximal tubular cells induced by TGF-beta(1) through the ERK1/2 and JNK MAPK pathways. Am J Physiol Renal Physiol 303: F757-F765, 2012. First published June 20, 2012; doi: 10.1152/ajprenal.00470.2011.-Heat shock protein (HSP) 47 is a collagen-specific molecular chaperone that is essential for the biosynthesis of collagen molecules. It is likely that increased levels of HSP47 contribute to the assembly of procollagen and thereby cause an excessive accumulation of collagens in disease processes associated with fibrosis. Although HSP47 promotes renal fibrosis, the underlying mechanism and associated signaling events have not been clearly delineated. We examined the role of HSP47 in renal fibrosis using a rat unilateral ureteral obstruction model and transforming growth factor (TGF)-beta(1)-treated human proximal tubular epithelial (HK-2) cells. An upregulation of HSP47 in both in vivo and 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 HSP47 by short interfering RNA suppressed the expression of ECM proteins and PAI-1. In addition, TGF-beta(1)-induced HSP47 expression in HK-2 cells was attenuated by ERK1/2 and JNK MAPK inhibitors. These data suggest that ERK1/2 and JNK signaling events are involved in modulating the expression of HSP47, the chaperoning effect of which on TGF-beta(1) would ultimately contribute to renal fibrosis by enhancing the synthesis and deposition of ECM proteins.
引用
收藏
页码:F757 / F765
页数:9
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