title: BMP signaling in rats with TNBS-induced colitis following BMP7 therapy.
abstract: Beyond stimulating bone formation, bone morphogenetic proteins (BMPs) are important in development, inflammation, and malignancy of the gut. We have previously shown that BMP7 has a regenerative, anti-inflammatory, and antiproliferative effect on experimental inflammatory bowel disease (IBD) in rats. To further investigate the BMP signaling pathway we monitored the effect of BMP7 therapy on the BMP signaling components in the rat colon during different stages of experimentally induced colitis by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The results showed a significantly decreased BMP7 expression in the acute phase, followed by a significantly increased BMP2 and decreased BMP6 expression during the chronic phase of colitis. BMP7 therapy influenced the expression of several BMPs with the most prominent effect on downregulation of BMP2 and upregulation of BMP4 in the chronic phase of colitis. Importantly, connective tissue growth factor and noggin expression were elevated in the acute stage and significantly decreased upon BMP7 therapy. BMP receptor I expression was unchanged, whereas BMP receptor II was decreased at day 2 and increased at days 14 and 30 of TNBS inflammation. However, an opposite pattern of expression following BMP7 therapy has been observed. BMP7 increased the expression of BR-Smad including Smad3 and Smad4. Inhibitory Smads were increased in colitis and significantly decreased following BMP7 therapy at later stages of the disease. We suggest that BMP signaling was altered during TNBS-induced colitis and was recovered with BMP7 administration, suggesting that IBD is a reversible process.
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia. ivanam@medri.hr
authors.forename: Ivana
authors.initials: I
authors.lastname: Maric
authors.forename: Natalia
authors.initials: N
authors.lastname: Kucic
authors.forename: Tamara
authors.initials: T
authors.lastname: Turk Wensveen
authors.forename: Ivana
authors.initials: I
authors.lastname: Smoljan
authors.forename: Blazenka
authors.initials: B
authors.lastname: Grahovac
authors.forename: Sanja
authors.initials: S
authors.lastname: Zoricic Cvek
authors.forename: Tanja
authors.initials: T
authors.lastname: Celic
authors.forename: Dragica
authors.initials: D
authors.lastname: Bobinac
authors.forename: Slobodan
authors.initials: S
authors.lastname: Vukicevic
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis; D055415:Bone Morphogenetic Protein 4 / Q000096:biosynthesis; D055418:Bone Morphogenetic Protein 6 / Q000096:biosynthesis; D055419:Bone Morphogenetic Protein 7 / Q000096:biosynthesis / Q000627:therapeutic use*; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000096:biosynthesis; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000096:biosynthesis; D002352:Carrier Proteins / Q000096:biosynthesis; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis; D004195:Disease Models, Animal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000096:biosynthesis; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity; D000099176:Noggin Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D055418:Bone Morphogenetic Protein 6; D055419:Bone Morphogenetic Protein 7; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D002352:Carrier Proteins; D055513:Connective Tissue Growth Factor; D051785:Smad Proteins; D014302:Trinitrobenzenesulfonic Acid; D000099176:Noggin Protein; C525720:Bmp2 protein, rat; C525811:Bmp4 protein, rat; C525818:Bmp6 protein, rat; C525821:Bmp7 protein, rat; C526316:CCN2 protein, rat