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Effects of in vivo administration of BMP-7 to expression levels of BMP-2 in experimental inflammatory bowel disease

作者
Ivana Marić,Sanja Zoričić Cvek,Tanja Ćelić,Tamara Turk Wensveen,Željka Crnčević-Orlić,Dragica Bobinac
出处
期刊:Bone [Elsevier BV]
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摘要

Bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta(TGF-beta ) superfamily, are multifunctional cytokines originally isolated from the bone. Beside their primarily osteogenic function documented by new bone formation their importance in development, proliferation and morphogenesis on a variety of cells and tissues has been shown. BMP2 and BMP7 are BMP family members with 60% similarity at the amino acid sequence. They are expressed in many tissues though their role is best understood in the bone. More recently it has been shown that BMP2 and BMP7, their receptors and BMP associated signaling molecules are expressed in non-skeletal organs e.g. kidneys, lungs, heart, intestine, eyes, and brain. Different levels of expression and mutations of these molecules were observed in organ diseases as well as in carcinomas. Using immunohistochemistry, we have previously shown the presence of BMP2 and BMP7 in colon tissues. The aim of this study was to investigate the expression level of mRNA for BMP2 and BMP7 in rat colons during different phases of experimental inflammatory disease as well as the effect of BMP7 treatment on endogenous expression of BMP2 and BMP7. Experimental colitis was induced by intracolonic administration of the clysma containing 2, 4, 6-trinitrobenzensulphonic acid (TNBS). We study the mRNA expression level of BMP2 and BMP7 during acute (2nd and 5th day after colitis induction) and chronic phase (14th and 30th after colitis induction) of experimental colitis as well as after BMP7 treatment with RT-PCR. RT-PCR analysis confirmed immunohistochemical data of the presence of BMP2 and BMP7 during acute and chronic phases of experimental inflammatory bowel disease. Expression of BMP2 and BMP7 was observed during the acute as well the chronic phase of colitis. Levels of BMP2 were gradually increased from days 2 to 30 after colitis induction while levels of BMP7 were increased at days 14 and 30. BMP7 treatment reduced the expression level of transcript for BMP2 in colon tissue during experimental colitis. Presence of BMP2 and BMP7 expressions in colon tissue during inflammatory bowel disease suggests an important role of BMP members in the regulation of colon tissue damage and healing. Their different pattern of expression indicated on potential tension between these BMP members might have therapeutic benefit (potential) for intestine diseases as was shown for kidney disease. Analysis of the BMP family members in colon tissue especially BMP-6 may contribute to the better understanding of the role and interplay of BMPs in inflammatory bowel disease.

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