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.
Highlights
Crohn’s Disease (CD) is a chronic inflammatory pathology of the gut that in a significant proportion of patients, leads to complications related to the development of intestinal fibrosis and strictures that often need a surgical intervention.Genetic studies identified several single nucleotide polymorphisms (SNPs) associated with CD in genes related to autophagy, a cellular process essential in intestinal homeostasis [1]
We reported that autophagy is reduced in the damaged mucosa of CD patients [2] and that autophagy stimulation prevents intestinal inflammation [3]
Control of inflammation by the current therapies does not seem enough to prevent fibrosis and both anti- and pro-fibrotic effects have been attributed to autophagy stimulation in different organic systems [4,5]
Summary
Crohn’s Disease (CD) is a chronic inflammatory pathology of the gut that in a significant proportion of patients, leads to complications related to the development of intestinal fibrosis and strictures that often need a surgical intervention.Genetic studies identified several single nucleotide polymorphisms (SNPs) associated with CD in genes related to autophagy, a cellular process essential in intestinal homeostasis [1]. Crohn’s Disease (CD) is a chronic inflammatory pathology of the gut that in a significant proportion of patients, leads to complications related to the development of intestinal fibrosis and strictures that often need a surgical intervention. We reported that autophagy is reduced in the damaged mucosa of CD patients [2] and that autophagy stimulation prevents intestinal inflammation [3]. Control of inflammation by the current therapies does not seem enough to prevent fibrosis and both anti- and pro-fibrotic effects have been attributed to autophagy stimulation in different organic systems [4,5]. We aim to analyze the effects of pharmacological modulation of autophagy in the development of intestinal fibrosis
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