BMP signaling in rats with TNBS-induced colitis following BMP7 therapy
BMP signaling in rats with TNBS-induced colitis following BMP7 therapy
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DOI：
10.1152/ajpgi.00244.2011
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发表时间：
2012-05-01
影响因子：
4.5
通讯作者：
Vukicevic, Slobodan
中科院分区：
文献类型：
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作者：
Maric, Ivana;Kucic, Natalia;Vukicevic, Slobodan
Maric I，Kucic N，Turk Wensveen T，Smoljan I，Grahovac B，Zoricic Cvek S，Celic T，Bobinac D，Vukicevic S. BMP 7治疗后TNBS诱导的结肠炎大鼠中的BMP信号传导。美国生理学杂志胃肠和肝脏生理学302：G1151-G1162，2012年。首次发表于2012年2月23日; doi：10.1152/ajpgi.00244.2011。除了刺激骨形成，骨形态发生蛋白（BMP）在肠道发育、炎症和恶性肿瘤中也很重要。我们之前已经证明，BMP 7对大鼠实验性炎症性肠病（IBD）具有再生，抗炎和抗增殖作用。为了进一步研究BMP信号传导途径，我们监测了在由2，4，6-三硝基苯磺酸（TNBS）实验诱导的结肠炎的不同阶段期间BMP 7治疗对大鼠结肠中BMP信号传导组分的影响。结果显示，在急性期BMP 7表达显著降低，随后在结肠炎慢性期BMP 2表达显著增加，BMP 6表达降低。BMP 7治疗影响了几种BMPs的表达，其中对结肠炎慢性期中BMP 2的下调和BMP 4的上调的影响最显著。重要的是，结缔组织生长因子和头蛋白表达在急性期升高，并在BMP 7治疗后显著降低。BMP受体I的表达没有变化，而BMP受体II在TNBS炎症第2天减少，在第14和30天增加。然而，已经观察到BMP 7治疗后的相反表达模式。BMP 7可增加BR-Smad（包括Smad 3和Smad 4）的表达。抑制性Smads在结肠炎中增加，并且在疾病的后期阶段在BMP 7治疗后显著降低。我们认为，BMP信号在TNBS诱导的结肠炎过程中发生了改变，并在BMP 7给药后恢复，这表明IBD是一个可逆的过程。
Maric I, Kucic N, Turk Wensveen T, Smoljan I, Grahovac B, Zoricic Cvek S, Celic T, Bobinac D, Vukicevic S. BMP signaling in rats with TNBS-induced colitis following BMP7 therapy. Am J Physiol Gastrointest Liver Physiol 302: G1151-G1162, 2012. First published February 23, 2012; doi:10.1152/ajpgi.00244.2011.-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.