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

Hong bo Xiao, Rui hong Liu, Guang hui Ling, Li Xiao, Yuan chen Xia, Fu you Liu, Jun Li, Ying hong Liu, Qin kai Chen, Jin lei Lv, Ming Zhan, Shi kun Yang, Yashpal S. Kanwar, Lin Sun*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

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)-β1-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-β1-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-β1 would ultimately contribute to renal fibrosis by enhancing the synthesis and deposition of ECM proteins.

Original languageEnglish (US)
Pages (from-to)F757-F765
JournalAmerican Journal of Physiology - Renal Physiology
Volume303
Issue number5
DOIs
StatePublished - Sep 1 2012

Keywords

  • C-jun NH2-terminal kinase
  • Extracellular signal-regulated protein kinase 1/2
  • Fibrosis
  • Heat shock protein 47
  • Mitogen-activated protein kinase
  • Renal proximal tubular cell
  • Transforming growth factor-β1

ASJC Scopus subject areas

  • Physiology
  • Urology

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