BMP signaling pathway in experimental inflammatory bowel disease

Abstract

Beyond stimulating bone formation, the 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 anti- proliferative effect on experimental inflammatory bowel disease (IBD) in rat. To further investigate the BMP signaling pathway we monitored the effect of BMP7 therapy on the BMP signaling components in rat colon during different stages of experimentally induced colitis by 2, 4, 6- trinitrobenzene sulfonic acid (TNBS). The results showed increased of BMP2 and -7 expression in the chronic phase of colitis. BMP7 treatment slightly enhanced BMP4, -6 and -7, and suppressed the BMP2 expression. CTGF and noggin expression was elevated in TNBS colitis, and slightly decreased upon BMP7 therapy. BMP receptor I expression was unchanged, while BMP receptor II was increased at day 14 and 30 of TNBS inflammation, and decreased following BMP7 therapy. BMP7 increased Smad1, Smad3 and Smad4. Inhibitory Smads were increased in colitis, but not in rats treated with BMP7. We conclude that BMP signaling is preserved in colon during TNBS-induced colonic inflammation and could be modulated with BMP7, suggesting that IBD is a reversible process with self-recovery features.