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‐β 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‐β, ICAM‐1) and pro‐fibrogenic (TGF‐β) 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. J. Cell. Physiol. 196: 258–264, 2003. © 2003 Wiley‐Liss, Inc.