Blockade of TGF-β accelerates mucosal destruction through epithelial cell apoptosis
Blockade of TGF-β accelerates mucosal destruction through epithelial cell apoptosis
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DOI：
10.1016/j.bbrc.2007.05.117
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发表时间：
2007-08-03
影响因子：
3.1
通讯作者：
Nakane, Akio
中科院分区：
文献类型：
--
作者：
Sakuraba, Hirotake;Ishiguro, Yoh;Nakane, Akio
为了阐明转化生长因子（TGF）-β对体内肠上皮损伤的保护作用，通过结肠切片的组织学分析（包括凋亡的上皮细胞），评估了抗TGF-β抗体对葡聚糖硫酸钠（DSS）诱导的结肠炎中上皮破坏和细胞凋亡的影响。为了评估上皮细胞凋亡的途径，我们分析了上皮细胞中半胱天冬酶的活性、Fas 的水平和细胞 FLICE 抑制蛋白 (cFLIP) 的表达。在 DSS 诱导的结肠炎溃疡发生之前，凋亡上皮细胞增加，TGF-β 的中和加剧了上皮细胞凋亡和组织学损伤评分。在抗 TGF-β 抗体处理的小鼠肠上皮细胞中观察到 caspase-8 活性和 Fas 表达上调以及 cFLIP 表达减少。本研究表明，抑制TGF-β会恶化上皮细胞凋亡，而凋亡上皮细胞的增加可能会加剧肠粘膜的炎症。 (c) 2007 年，爱思唯尔公司出版。
To clarify the protective role of transforming growth factor (TGF)-beta for the intestinal epithelial injury in vivo, the effect of antibodies against TGF-beta on epithelial destruction and apoptosis was assessed in dextran sulfate sodium (DSS)-induced colitis by histological analysis of colonic sections, account of apoptotic epithelial cells. To evaluate the pathways of epithelial apoptosis, we analyzed the activities of caspases, the level of Fas and cellular FLICE-inhibitory protein (cFLIP) expression in epithelial cells. Apoptotic epithelial cells were increased prior to the onset of ulceration in DSS-induced colitis, and the neutralization of TGF-beta exacerbated epithelial apoptosis and histological damage score. The up-regulation of caspase-8 activity and Fas expression and reduced cFLIP expression were observed in intestinal epithelial cells from anti-TGF-beta antibody-treated mice. The present study revealed that suppression of TGF-beta deteriorated epithelial apoptosis, and the increase of apoptotic epithelial cells may amplify the inflammation in gut mucosa. (c) 2007 Published by Elsevier Inc.