Autophagy Stimulation as a Potential Strategy Against Intestinal Fibrosis

Cells. 2019 Sep 13;8(9):1078. doi: 10.3390/cells8091078.

Abstract

We recently observed reduced autophagy in Crohn's disease patients and an anti-inflammatory effect of autophagy stimulation in murine colitis, but both anti- and pro-fibrotic effects are associated with autophagy stimulation in different tissues, and fibrosis is a frequent complication of Crohn's disease. Thus, we analyzed the effects of pharmacological modulation of autophagy in a murine model of intestinal fibrosis and detected that autophagy inhibition aggravates, while autophagy stimulation prevents, fibrosis. These effects are associated with changes in inflammation and in collagen degradation in primary fibroblasts. Thus, pharmacological stimulation of autophagy may be useful against intestinal fibrosis.

Keywords: autophagy; inflammation; intestinal fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / drug effects*
  • Collagen / metabolism
  • Crohn Disease / complications
  • Disease Models, Animal
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Fibrosis / drug therapy*
  • Immunosuppressive Agents / pharmacology*
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Intestines / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Sirolimus / pharmacology

Substances

  • Immunosuppressive Agents
  • Collagen
  • Sirolimus