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RESEARCH PRODUCT

Decreased Fibrogenesis After Treatment with Pirfenidone in a Newly Developed Mouse Model of Intestinal Fibrosis

Franz E. WeberSilvia LangGerhard RoglerChristian LutzGabi BollmannAnouk HünerwadelMartin HausmannStefania FagagniniAlexander TchouboukovCéline MamieRemo MeierAchim WeberJesus Cosin-roger

subject

0301 basic medicinemedicine.medical_specialtyPyridonesBlotting Western610 Medicine & healthGastroenterologyImmunoenzyme TechniquesMice03 medical and health sciencesIdiopathic pulmonary fibrosis0302 clinical medicineTransforming Growth Factor betaFibrosis10049 Institute of Pathology and Molecular PathologyInternal medicinemedicineAnimalsImmunology and Allergy2715 GastroenterologyCell ProliferationMice Inbred BALB CbiologyCell growthbusiness.industryAnti-Inflammatory Agents Non-SteroidalGastroenterologyPirfenidoneTransforming growth factor betamedicine.diseaseFibrosisMice Inbred C57BLTransplantationBlotDisease Models AnimalIntestinal Diseases10219 Clinic for Gastroenterology and Hepatology030104 developmental biology2723 Immunology and Allergybiology.proteinFemale030211 gastroenterology & hepatologyCollagen10069 Clinic of Cranio-Maxillofacial SurgerybusinessAfter treatmentmedicine.drug

description

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.

yearjournalcountryeditionlanguage
2016-03-01Inflammatory Bowel Diseases
https://doi.org/10.1097/mib.0000000000000716