Bone morphogenetic protein-7 reduces the severity of colon tissue damage and accelerates the healing of inflammatory bowel disease in rats.

ABSTRACT

Bone morphogenetic protein-7 (BMP-7) is a growth and differentiation factor and belongs to the TGF-beta superfamily of proteins. Previous studies have shown an abundant expression of BMP-7 in the developing intestine and an association with a perturbed BMP/SMAD downstream signaling leading to a malignant phenotype and inflammation in the gut. In the present study, we have evaluated the effect of systemically administered recombinant human BMP-7 against trinitrobenzenesulfonic (TNBS) acid induced inflammatory bowel disease (IBD) in rats. The TNBS administered rats treated with BMP-7 have developed much less severe form of colitis based on macroscopic and histological scoring when administered 1.5 h before or 24 h after colitis induction. Bioavailability studies in healthy rats have revealed that significant portion (3.6%) of i.v. administered BMP-7 is targeted for BMP-7 receptors in the stomach and ileum, respectively, suggesting its availability to target tissue upon administration. Immunohistochemical and RT-PCR analyses have shown elevated expression of pro-inflammatory (IL-6, TNF-beta, ICAM-1) and pro-fibrogenic (TGF-beta) cytokines, and BMP-7 treatment significantly reduced their expression in the intestine; among which the suppression of IL-6 appeared to be the most important. Taken together, the results of this study suggest that BMP-7 plays an important role in the regulation of anti-inflammatory response in the adult gut tissue.