Bone morphogenetic protein-7 reduces the severity of colon tissue damage and accelerates the healing of inflammatory bowel disease in rats.
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.
Maric
Ivana
I
Department of Anatomy, Medical School University of Rijeka, Croatia.
Poljak
Ljiljana
L
Zoricic
Sanja
S
Bobinac
Dragica
D
Bosukonda
Dattatreyamurty
D
Sampath
Kuber T
KT
Vukicevic
Slobodan
S
D030201:Activin Receptors, Type I / Q000235:genetics; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism* / Q000493:pharmacokinetics; D003106:Colon / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D015536:Down-Regulation; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000473:pathology* / Q000503:physiopathology* / Q000517:prevention & control; D007275:Injections, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017978:Receptors, Growth Factor; D012720:Severity of Illness Index; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014945:Wound Healing / Q000502:physiology*
C525819:BMP7 protein, human; C525821:Bmp7 protein, rat; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D015850:Interleukin-6; D011506:Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; C508960:TGFB1 protein, human; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D017346:Protein Serine-Threonine Kinases; C425423:ACVR1 protein, human; D030201:Activin Receptors, Type I; D052005:Bone Morphogenetic Protein Receptors, Type I