CSA13 inhibits colitis-associated intestinal fibrosis via a formyl peptide receptor like-1 mediated HMG-CoA reductase pathway.

摘要: Many Crohn's disease (CD) patients develop intestinal strictures, which are difficult to prevent and treat. Cationic steroid antimicrobial 13 (CSA13) shares cationic nature function with peptide cathelicidin. As many functions of cathelicidin mediated through formyl receptor-like 1 (FPRL1), we hypothesize that CSA13 mediates anti-fibrogenic effects via FPRL1. Human biopsies were used in clinical data analysis. Chronic trinitrobenzene sulfonic acid (TNBS) colitis-associated fibrosis mouse model the administration was used. Colonic FPRL1 mRNA expression positively correlated histology scores inflammatory bowel patients. In CD patients, colonic stricture. ameliorated without influencing microbiota. Inhibition FPRL1, but not suppression microbiota, reversed these protective CSA13. Metabolomic analysis indicated increased fecal mevalonate levels TNBS-treated mice, reduced by administration. inhibited HMG-CoA reductase activity an FPRL1-dependent manner. Mevalonate effect The is associated severe mucosal inhibits modulation pathway.