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Erschienen in:
10.01.2022 | Original Article
Resolvin D1 Prevents Epithelial-to-Mesenchymal Transition and Reduces Collagen Deposition by Stimulating Autophagy in Intestinal Fibrosis
Erschienen in: Digestive Diseases and Sciences | Ausgabe 10/2022
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Background
Intestinal fibrosis is the most common complication of inflammatory bowel disease; nevertheless, specific therapies are still unavailable. Resolvin D1 (RvD1), a typical endogenous ω-3 fatty acid-derived lipid mediator, has attracted wide attention due to its remarkable anti-fibrosis effects. However, the efficacy and mechanisms of RvD1 in intestinal fibrosis remain unclear.
Aim
To investigate the protective effect of RvD1 in a dextran sulfate sodium (DSS)-induced intestinal fibrosis model and explore the molecular mechanisms underlying its anti-fibrotic effect.
Methods
A DSS-induced intestinal fibrosis model and intestinal epithelial-to-mesenchymal transition (EMT) model were used to observe the efficacy of RvD1, and fibroblasts were stimulated with conditioned medium with or without TGF-β1 to investigate the probable mechanisms of RvD1 in intestinal fibrosis disease.
Results
Intestinal fibrosis was effectively alleviated by RvD1 in a DSS-induced model, both preventively and therapeutically, and autophagy inhibition-induced EMT in intestinal epithelial cells was significantly suppressed in vivo and in vitro. Furthermore, RvD1 reduced epithelial cell EMT paracrine signaling, which promoted the differentiation of local fibroblasts into myofibroblasts.
Conclusions
Our results suggested that RvD1 reduces autophagy-induced EMT in intestinal epithelial cells and ameliorates intestinal fibrosis by disrupting epithelial–fibroblast crosstalk.