engleski

Expression patterns of bone morphogenetic proteins and Smad proteins in inflammatory bowel disease

Bone morphogenetic proteins (BMPs), members of the transforming growth factor- (TGF-) superfamily, are multifunctional cytokines originally isolated from the bone. Along with their primarily osteogenic function their importance in development, proliferation and morphogenesis on a variety of cells and tissues has been shown as well as their association with healing processes of different non-skeletal tissues and organs. BMPs are expressed in many tissues though their role is best understood in the bone. Alterations in BMPs expression and BMP signaling pathway have been associated with the pathological conditions linked to several human diseases such as inflammatory bowel disease (IBD) and colon cancers. The aim of this study was to investigate the potential involvement of BMPs in inflammatory bowel disease by the continuous monitoring of the expression level of BMPs and their signaling molecules in rat colons during different phases of experimental IBD as well as after BMP7 treatment. IBD was induced by intrarectal administration of trinitrobenzenesulfonic acid (TNBS). After the IBD induction, the rats were treated with BMP-7 (100 g/ml) and sacrificed on the 2nd, 5th, 14th, and 30th day after the TNBS induction. Expression levels of BMPs and their signaling molecules (Smad proteins) were determined by RT-PCR and immunohistochemical analyses. During IBD the expression of BMPs was present in colon samples with a slight incensement of BMP-2 and BMP-7 expression in the chronic phase of the disease. BMP-7 treatment moderately enhanced expression of BMP-4, -6 and -7 and suppressed the BMP-2 expression. Further, we found increased expression of BMP-specific R-Smads (BR-Smads) during IBD as well as after BMP-7 treatment and increased expression of activin/TGF-beta specific R-Smads (AR-Smads) especially after BMP-7 treatment. Expression of Smad4 as Co-Smad was unchanged during diseases as well as after BMP-7 treatment. Furthermore, the expression levels of inhibitory Smads (Smad6 and Smad7) were increased in colon samples from diseased animals in comparison with the colon of animals treated with BMP-7. The expression pattern of BMPs and Smad proteins during IBD as well as after BMP-7 treatment suggests an important role of BMPs in the regulation of colon tissue damage and healing during disease.

Bone morphogenetic proteins; Smad proteins; Inflammatory bowel disease

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