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

Anke Nijhuis, Paolo Biancheri, Amy Lewis, Cleo L. Bishop, Paolo Giuffrida, Christopher Chan, Roger Feakins, Richard Poulsom, Antonio Di Sabatino, Gino Roberto Corazza, Thomas T. MacDonald, James O. Lindsay, Andrew R. Silver

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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.

Original languageEnglish
Pages (from-to)341-350
Number of pages10
JournalClinical Science
Volume127
Issue number5
DOIs
Publication statusPublished - 2014

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MicroRNAs
Crohn Disease
Fibrosis
Collagen
Fibroblasts
Pathologic Constriction
Mucous Membrane
Down-Regulation
Transforming Growth Factors
Matrix Metalloproteinase 12
Biomarkers
Matrix Metalloproteinase 3
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase Inhibitors
Pulmonary Fibrosis
Proteins
Liver
Serum

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Nijhuis, A., Biancheri, P., Lewis, A., Bishop, C. L., Giuffrida, P., Chan, C., ... Silver, A. R. (2014). In Crohn's disease fibrosis-reduced expression of the miR-29 family enhances collagen expression in intestinal fibroblasts. Clinical Science, 127(5), 341-350. https://doi.org/10.1042/CS20140048

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.; Silver, Andrew R.

In: Clinical Science, Vol. 127, No. 5, 2014, p. 341-350.

Research output: Contribution to journalArticle

Nijhuis, A, Biancheri, P, Lewis, A, Bishop, CL, Giuffrida, P, Chan, C, Feakins, R, Poulsom, R, Di Sabatino, A, Corazza, GR, MacDonald, TT, Lindsay, JO & Silver, AR 2014, 'In Crohn's disease fibrosis-reduced expression of the miR-29 family enhances collagen expression in intestinal fibroblasts.', Clinical Science, vol. 127, no. 5, pp. 341-350. https://doi.org/10.1042/CS20140048
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. ; Silver, Andrew R. / In Crohn's disease fibrosis-reduced expression of the miR-29 family enhances collagen expression in intestinal fibroblasts. In: Clinical Science. 2014 ; Vol. 127, No. 5. pp. 341-350.
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