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.

• Authors: Ivana Maric, Ljiljana Poljak, Sanja Zoricic, Dragica Bobinac, Dattatreyamurty Bosukonda, Kuber T Sampath, Slobodan Vukicevic
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 196 Issue 2 Pg. 258-64 (Aug 2003) ISSN: 0021-9541 [Print] United States
• PMID: 12811818 (Publication Type: Journal Article)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• BMP7 protein, human
• Bmp7 protein, rat
• Bone Morphogenetic Protein 7
• Bone Morphogenetic Proteins
• Interleukin-6
• Proteins
• RNA, Messenger
• Receptors, Growth Factor
• TGFB1 protein, human
• Tgfb1 protein, rat
• Transforming Growth Factor beta
• Transforming Growth Factor beta1
• Tumor Necrosis Factor-alpha
• Intercellular Adhesion Molecule-1
• Protein Serine-Threonine Kinases
• ACVR1 protein, human
• Activin Receptors, Type I
• Bone Morphogenetic Protein Receptors, Type I

Topics

• Activin Receptors, Type I (genetics)
• Animals
• Bone Morphogenetic Protein 7
• Bone Morphogenetic Protein Receptors, Type I
• Bone Morphogenetic Proteins (administration & dosage, genetics, metabolism, pharmacokinetics)
• Colon (metabolism, pathology, physiopathology)
• Down-Regulation
• Gastric Mucosa (metabolism)
• Humans
• Inflammatory Bowel Diseases (pathology, physiopathology, prevention & control)
• Injections, Intravenous
• Intercellular Adhesion Molecule-1 (genetics)
• Interleukin-6 (genetics)
• Intestinal Mucosa (metabolism)
• Protein Serine-Threonine Kinases
• Proteins
• RNA, Messenger (antagonists & inhibitors, metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Growth Factor
• Severity of Illness Index
• Time Factors
• Transforming Growth Factor beta (genetics)
• Transforming Growth Factor beta1
• Tumor Necrosis Factor-alpha (genetics)
• Wound Healing (physiology)