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Decreased fibrogenesis after treatment with pirfenidone in a newly developed mouse model of intestinal fibrosis


Meier, Remo; Lutz, Christian; Cosín-Roger, Jesus; Fagagnini, Stefania; Bollmann, Gabi; Hünerwadel, Anouk; Mamie, Celine; Lang, Silvia; Tchouboukov, Alexander; Weber, Franz E; Weber, Achim; Rogler, Gerhard; Hausmann, Martin (2016). Decreased fibrogenesis after treatment with pirfenidone in a newly developed mouse model of intestinal fibrosis. Inflammatory Bowel Diseases, 22(3):569-582.

Abstract

BACKGROUND Fibrosis as a common problem in patients with Crohn's disease is a result of an imbalance toward excessive tissue repair. At present, there is no specific treatment option. Pirfenidone is approved for the treatment of idiopathic pulmonary fibrosis with both antifibrotic and anti-inflammatory effects. We subsequently investigated the impact of pirfenidone treatment on development of fibrosis in a new mouse model of intestinal fibrosis.
METHODS Small bowel resections from donor mice were transplanted subcutaneously into the neck of recipients. Animals received either pirfenidone (100 mg/kg, three times daily, orally) or vehicle.
RESULTS After administration of pirfenidone, a significantly decreased collagen layer thickness was revealed as compared to vehicle (9.7 ± 1.0 versus 13.5 ± 1.5 µm, respectively, **P < 0.001). Transforming growth factor-β and matrix metalloproteinase-9 were significantly decreased after treatment with pirfenidone as confirmed by real-time PCR (0.42 ± 0.13 versus 1.00 ± 0.21 and 0.46 ± 0.24 versus 1.00 ± 0.62 mRNA expression level relative to GAPDH, respectively, *P < 0.05). Significantly decreased transforming growth factor-β after administration of pirfenidone was confirmed by Western blotting.
CONCLUSION In our mouse model, intestinal fibrosis can be reliably induced and is developed within 7 days. Pirfenidone partially prevented the development of fibrosis, making it a potential treatment option against Crohn's disease-associated fibrosis.

Abstract

BACKGROUND Fibrosis as a common problem in patients with Crohn's disease is a result of an imbalance toward excessive tissue repair. At present, there is no specific treatment option. Pirfenidone is approved for the treatment of idiopathic pulmonary fibrosis with both antifibrotic and anti-inflammatory effects. We subsequently investigated the impact of pirfenidone treatment on development of fibrosis in a new mouse model of intestinal fibrosis.
METHODS Small bowel resections from donor mice were transplanted subcutaneously into the neck of recipients. Animals received either pirfenidone (100 mg/kg, three times daily, orally) or vehicle.
RESULTS After administration of pirfenidone, a significantly decreased collagen layer thickness was revealed as compared to vehicle (9.7 ± 1.0 versus 13.5 ± 1.5 µm, respectively, **P < 0.001). Transforming growth factor-β and matrix metalloproteinase-9 were significantly decreased after treatment with pirfenidone as confirmed by real-time PCR (0.42 ± 0.13 versus 1.00 ± 0.21 and 0.46 ± 0.24 versus 1.00 ± 0.62 mRNA expression level relative to GAPDH, respectively, *P < 0.05). Significantly decreased transforming growth factor-β after administration of pirfenidone was confirmed by Western blotting.
CONCLUSION In our mouse model, intestinal fibrosis can be reliably induced and is developed within 7 days. Pirfenidone partially prevented the development of fibrosis, making it a potential treatment option against Crohn's disease-associated fibrosis.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
04 Faculty of Medicine > Center for Dental Medicine > Clinic for Cranio-Maxillofacial Surgery
04 Faculty of Medicine > University Hospital Zurich > Clinic for Gastroenterology and Hepatology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:March 2016
Deposited On:17 May 2016 09:22
Last Modified:08 Dec 2017 19:30
Publisher:Lippincott Williams & Wilkins
ISSN:1078-0998
Publisher DOI:https://doi.org/10.1097/MIB.0000000000000716
PubMed ID:26848518

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