TRAP1 ameliorates renal tubulointerstitial fibrosis in mice with unilateral ureteral obstruction by protecting renal tubular epithelial cell mitochondria

FASEB J. 2017 Oct;31(10):4503-4514. doi: 10.1096/fj.201700283R. Epub 2017 Jul 14.

Abstract

Mitochondrial dysfunction causes renal tubular epithelial cell injury and promotes cell apoptosis and renal tubulointerstitial fibrosis (TIF) progression. TNF receptor-associated protein 1 (TRAP1) is a molecular chaperone protein that is localized in mitochondria. It plays an important role in cell apoptosis; however, its functional mechanism in TIF remains unclear. In this study, we observed the effects of TRAP1 in renal tubular epithelial cell mitochondria in mice with unilateral ureteral obstruction and its function in cell apoptosis and TIF. Results show that TRAP1 could protect the mitochondrial structure in renal tubular epithelial cells; maintain the levels of mitochondrial membrane potential, ATP, and mitochondrial DNA copy number; inhibit reactive oxygen species production; stabilize the expression of the mitochondrial inner membrane protein mitofilin; reduce renal tubular epithelial cell apoptosis; and inhibit TIF. These results provide new theoretical foundations for additional understanding of the antifibrotic mechanism of TRAP1 in the kidney.-Chen, J.-F., Wu, Q.-S., Xie, Y.-X., Si, B.-L., Yang, P.-P., Wang, W.-Y., Hua, Q., He, Q. TRAP1 ameliorates renal tubulointerstitial fibrosis in mice with unilateral ureteral obstruction by protecting renal tubular epithelial cell mitochondria.

Keywords: apoptosis; extracellular matrix; mitochondrial DNA; mitofilin; reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Fibrosis / drug therapy
  • Fibrosis / metabolism
  • HSP90 Heat-Shock Proteins / metabolism*
  • Kidney Tubules / drug effects
  • Kidney Tubules / metabolism*
  • Kidney Tubules / pathology
  • Male
  • Mice, Inbred C57BL
  • Mitochondria / metabolism*
  • Protective Agents / pharmacology
  • Reactive Oxygen Species / metabolism
  • Ureteral Obstruction / metabolism*
  • Ureteral Obstruction / pathology

Substances

  • HSP90 Heat-Shock Proteins
  • Protective Agents
  • Reactive Oxygen Species
  • TRAP-1 protein, mouse