Autophagy Stimulation as a Potential Strategy Against Intestinal Fibrosis

• Published in: Cells (Basel, Switzerland) Vol. 8; no. 9; p. 1078
• Main Authors: Cosin-Roger, Jesus, Canet, Francisco, Macias-Ceja, Dulce C., Gisbert-Ferrándiz, Laura, Ortiz-Masiá, Dolores, Esplugues, Juan V., Alós, Rafael, Navarro, Francisco, Barrachina, María D., Calatayud, Sara
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13.09.2019; MDPI
• Subjects: Animal models; Animals; Autophagy; Autophagy - drug effects; Brief Report; Colitis; Collagen; Collagen - metabolism; Colon; Crohn Disease - complications; Crohn's disease; Cytokines; Disease Models, Animal; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; Fibrosis; Fibrosis - drug therapy; Gene expression; Immunosuppressive Agents - pharmacology; Inflammation; Inflammation - drug therapy; Inflammation - immunology; Inflammatory bowel diseases; intestinal fibrosis; Intestine; Intestines - pathology; Mice; Mice, Inbred C57BL; Phagocytosis; Proteins; Sirolimus - pharmacology; Software; Variance analysis; Spain; intestinal fibrosis; inflammation; autophagy
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells8091078

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.