In Crohn's disease fibrosis-reduced expression of the miR-29 family enhances collagen expression in intestinal fibroblasts

Nijhuis, Anke, Biancheri, Paolo, Lewis, Amy, Bishop, Cleo L, Giuffrida, Paolo, Chan, Christopher, Feakins, Roger, Poulsom, Richard, Di Sabatino, Antonio, Corazza, Gino Roberto, MacDonald, Thomas T, Lindsay, James O and Silver, Andrew R (2014) In Crohn's disease fibrosis-reduced expression of the miR-29 family enhances collagen expression in intestinal fibroblasts. Clinical Science, 127 (5). pp. 341-350. ISSN 0143-5221

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Abstract

Intestinal fibrosis with stricture formation is a complication of CD (Crohn's disease) that may mandate surgical resection. Accurate biomarkers that reflect the relative contribution of fibrosis to an individual stricture are an unmet need in managing patients with CD. The miRNA-29 (miR-29) family has been implicated in cardiac, hepatic and pulmonary fibrosis. In the present study, we investigated the expression of miR-29a, miR-29b and miR-29c in mucosa overlying a stricture in CD patients (SCD) paired with mucosa from non-strictured areas (NSCD). There was significant down-regulation of the miR-29 family in mucosa overlying SCD compared with mucosa overlying NSCD. miR-29b showed the largest fold-decrease and was selected for functional analysis. Overexpression of miR-29b in CD fibroblasts led to a down-regulation of collagen I and III transcripts and collagen III protein, but did not alter MMP (matrix metalloproteinase)-3, MMP-12 and TIMP (tissue inhibitor of metalloproteinase)-1 production. TGF (transforming growth factor)-β1 up-regulated collagen I and III transcripts and collagen III protein as a consequence of the down-regulation of miR-29b, and TGF-β1-induced collagen expression was reversed by exogenous overexpression of miR-29b. Furthermore, serum levels of miR-29 were lower in patients with stricturing disease compared with those without. These findings implicate the miR-29 family in the pathogenesis of intestinal fibrosis in CD and provide impetus for the further evaluation of the miR-29 family as biomarkers.

Item Type: Article
Uncontrolled Keywords: adolescent,adult,aged,biosynthesis,biosynthesis,metabolism,genetics,down-regulation,fibrosis,humans,metabolism,biosynthesis,middle aged,pharmacology,up-regulation
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: LivePure Connector
Date Deposited: 07 Aug 2018 16:30
Last Modified: 22 Apr 2020 06:56
URI: https://ueaeprints.uea.ac.uk/id/eprint/67975
DOI: 10.1042/CS20140048

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