Regulation of autophagy by TGF-β: emerging role in kidney fibrosis

Semin Nephrol. 2014 Jan;34(1):62-71. doi: 10.1016/j.semnephrol.2013.11.009. Epub 2013 Nov 22.

Abstract

Autophagy is a highly conserved homoeostatic mechanism for cell survival under conditions of stress, and is widely implicated as an important pathway in many biological processes and diseases. In progressive kidney diseases, fibrosis represents the common pathway to end-stage kidney failure. Transforming growth factor-β1 (TGF-β1) is a pleiotropic cytokine that has been established as a central mediator of kidney fibrosis. A recently emerging body of evidence from studies in renal cells in culture and experimental animal models suggests that TGF-β1 regulates autophagy and that autophagy regulates many critical aspects of normal and disease conditions associated with kidney fibrosis, such as tubulointerstitial fibrosis, glomerulosclerosis, and diabetic nephropathy. Here, we review the recent advances exploring the process of autophagy, its regulation by TGF-β1, and the implication in the pathogenesis of progressive kidney fibrosis and injury responses. Understanding the cellular and molecular bases of this process is crucial for identifying potential new diagnostic and therapeutic targets of kidney fibrosis.

Keywords: Autophagy; chronic kidney disease; fibrosis; transforming growth factor-β1.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Autophagy / physiology*
  • Diabetic Nephropathies / pathology
  • Fibrosis
  • Humans
  • Kidney / pathology*
  • Kidney Tubules / pathology
  • Mesangial Cells / pathology
  • Proteinuria / pathology
  • Signal Transduction / physiology
  • Transforming Growth Factor beta / physiology*

Substances

  • Transforming Growth Factor beta