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.
Skip Nav Destination
Article navigation
Research Article|
May 15 2014
In Crohn's disease fibrosis-reduced expression of the miR-29 family enhances collagen expression in intestinal fibroblasts
Anke Nijhuis;
Anke Nijhuis
*Centre for Digestive Diseases and National Centre for Bowel Research and Surgical Innovation, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, U.K.
Search for other works by this author on:
Paolo Biancheri;
Paolo Biancheri
1
†Centre for Immunology and Infectious Disease, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, U.K.
Search for other works by this author on:
Amy Lewis;
Amy Lewis
1
*Centre for Digestive Diseases and National Centre for Bowel Research and Surgical Innovation, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, U.K.
Search for other works by this author on:
Cleo L. Bishop;
Cleo L. Bishop
‡Centre for Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, U.K.
Search for other works by this author on:
Paolo Giuffrida;
Paolo Giuffrida
†Centre for Immunology and Infectious Disease, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, U.K.
Search for other works by this author on:
Christopher Chan;
Christopher Chan
§Academic Surgery Unit, Royal London Hospital, London, U.K.
Search for other works by this author on:
Roger Feakins;
Roger Feakins
¶Department of Cellular Pathology, Royal London Hospital, London, U.K.
Search for other works by this author on:
Richard Poulsom;
Richard Poulsom
*Centre for Digestive Diseases and National Centre for Bowel Research and Surgical Innovation, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, U.K.
Search for other works by this author on:
Antonio Di Sabatino;
Antonio Di Sabatino
∥Department of Internal Medicine, S. Matteo Hospital, University of Pavia, Pavia, Italy
Search for other works by this author on:
Gino Roberto Corazza;
Gino Roberto Corazza
∥Department of Internal Medicine, S. Matteo Hospital, University of Pavia, Pavia, Italy
Search for other works by this author on:
Thomas T. MacDonald;
Thomas T. MacDonald
†Centre for Immunology and Infectious Disease, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, U.K.
Search for other works by this author on:
James O. Lindsay;
*Centre for Digestive Diseases and National Centre for Bowel Research and Surgical Innovation, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, U.K.
Correspondence: Professor Andrew R. Silver (email a.silver@qmul.ac.uk) or Dr James O. Lindsay (email james.lindsay@bartshealth.nhs.uk).
Search for other works by this author on:
Andrew R. Silver
*Centre for Digestive Diseases and National Centre for Bowel Research and Surgical Innovation, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, U.K.
Correspondence: Professor Andrew R. Silver (email a.silver@qmul.ac.uk) or Dr James O. Lindsay (email james.lindsay@bartshealth.nhs.uk).
Search for other works by this author on:
Clin Sci (Lond) (2014) 127 (5): 341–350.
Article history
Received:
January 17 2014
Revision Received:
February 26 2014
Accepted:
March 18 2014
Accepted Manuscript online:
March 18 2014
Citation
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; In Crohn's disease fibrosis-reduced expression of the miR-29 family enhances collagen expression in intestinal fibroblasts. Clin Sci (Lond) 1 September 2014; 127 (5): 341–350. doi: https://doi.org/10.1042/CS20140048
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.