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

J Cell Physiol. 2003 Aug;196(2):258-64. doi: 10.1002/jcp.10275.

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.

MeSH terms

  • Activin Receptors, Type I / genetics
  • Animals
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Protein Receptors, Type I
  • Bone Morphogenetic Proteins / administration & dosage
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • Bone Morphogenetic Proteins / pharmacokinetics
  • Colon / metabolism
  • Colon / pathology*
  • Colon / physiopathology
  • Down-Regulation
  • Gastric Mucosa / metabolism
  • Humans
  • Inflammatory Bowel Diseases / pathology*
  • Inflammatory Bowel Diseases / physiopathology*
  • Inflammatory Bowel Diseases / prevention & control
  • Injections, Intravenous
  • Intercellular Adhesion Molecule-1 / genetics
  • Interleukin-6 / genetics
  • Intestinal Mucosa / metabolism
  • Protein Serine-Threonine Kinases*
  • Proteins*
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / 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*

Substances

  • 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