Cyclosporine regulates intestinal epithelial apoptosis via TGF-β-related signaling
Cyclosporine regulates intestinal epithelial apoptosis via TGF-β-related signaling
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DOI：
10.1152/ajpgi.90608.2008
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发表时间：
2009-09-01
影响因子：
4.5
通讯作者：
Nakane, Akio
中科院分区：
文献类型：
--
作者：
Satoh, Yuki;Ishiguro, Yoh;Nakane, Akio
佐藤，石黑勇，樱叶H，川口S，平贺，福田S，中根A。环孢素通过转化生长因子-β相关信号调节肠上皮细胞凋亡。Am J Physiol胃肠病肝生理学297：G514-G519,2009。2009年7月16日首次出版；DOI：10.1152/ajpgi.90608.2008。-环孢素是一种有效的免疫调节剂，在治疗溃疡性结肠炎(UC)方面有良好的效果。我们分析了环孢素通过转化生长因子-β相关信号调节上皮细胞凋亡的机制，因为上皮细胞的凋亡和再生之间的平衡似乎是维持肠道内环境稳定的关键因素。为此，用4%葡聚糖硫酸钠(DSS)诱导大鼠结肠炎模型，观察环孢素和抗转化生长因子-β抗体的治疗效果。环孢素治疗可改善DSS诱导的结肠炎的体重减轻、粘膜破坏和上皮细胞凋亡。环孢素可上调结肠组织中转化生长因子-β的表达，增强上皮细胞中p-Smad2和cFlIP的表达，并抑制caspase-8的活性，但不抑制caspase-1或-9的活性。抗转化生长因子-β抗体治疗可减轻结肠上皮细胞中cFLIP的表达，减轻体重减轻和环孢素对粘膜的破坏。这些结果表明，环孢素可能通过上调转化生长因子-β相关信号来保护上皮细胞的凋亡。
Satoh Y, Ishiguro Y, Sakuraba H, Kawaguchi S, Hiraga H, Fukuda S, Nakane A. Cyclosporine regulates intestinal epithelial apoptosis via TGF-beta-related signaling. Am J Physiol Gastrointest Liver Physiol 297: G514-G519, 2009. First published July 16, 2009; doi: 10.1152/ajpgi.90608.2008.-Cyclosporine is a potent immunomodulator and has a beneficial effect in the treatment of ulcerative colitis (UC). We analyzed the mechanism of the effects of cyclosporine on the regulation of epithelial apoptosis via TGF-beta-related signaling, because the balance between the apoptosis and regeneration of epithelial cells seems to be a key factor to maintain the intestinal homeostasis. For this purpose, colitis was induced by treatment of 4% dextran sulfate sodium (DSS), and the effect of treatment with cyclosporine and anti-TGF-beta antibody was assessed. Treatment with cyclosporine ameliorated body weight loss, mucosal destruction, and epithelial apoptosis in DSS-induced colitis. Cyclosporine was shown to upregulate the expression of TGF-beta in the colonic tissue, enhance the expression of p-Smad2 and cFLIP in epithelial cells, and inhibit caspase-8 activity but not caspase-1 or -9. Upregulation of cFLIP in the colonic epithelial cells, amelioration of body weight loss, and mucosal destruction by cyclosporine were attenuated by anti-TGF-beta antibody treatment. These results indicated that cyclosporine could have a protective role against epithelial apoptosis associated with upregulation of TGF-beta-related signaling.