Protein kinase C iota in the intestinal epithelium protects against dextran sodium sulfate-induced colitis.
Protein kinase C iota in the intestinal epithelium protects against dextran sodium sulfate-induced colitis.
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DOI：
10.1002/ibd.21547
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发表时间：
2011-08
影响因子：
4.9
通讯作者：
Murray, Nicole R.
中科院分区：
文献类型：
--
作者：
Calcagno, Shelly R.;Li, Shuhua;Shahid, Muhammad W.;Wallace, Michael B.;Leitges, Michael;Fields, Alan P.;Murray, Nicole R.
关键词：
肠上皮的完整性对于吸收和保留液体和营养物质至关重要。肠上皮还在肠道细菌和身体的免疫监视之间提供屏障。因此，肠上皮屏障功能是至关重要的，并且肠上皮的破坏导致受损区域的快速修复。我们使用良好表征的结肠炎小鼠模型评估了肠上皮稳态和对上皮损伤的反应中对蛋白激酶C1（PKC 1）的需求。分析小鼠葡聚糖硫酸钠（DSS）治疗的临床、组织学和细胞效应。敲除肠上皮中的小鼠PKCι基因（Prkci）（Prkci KO小鼠）对正常结肠稳态没有影响，然而，Prkci KO小鼠对DSS诱导的结肠炎和死亡显著更敏感。在停用DSS后，Prkci KO小鼠表现出细胞凋亡、炎症和肠微血管损伤的持续增加，以及三叶因子3（TFF 3）表达的进行性丧失，三叶因子3是一种对肠伤口愈合重要的调节肽。HT-29细胞中PKC 1表达的敲低降低了伤口愈合和TFF 3表达，而外源性TFF 3的添加恢复了PKC 1耗尽的细胞中的伤口愈合。PKCι在肠上皮中的表达保护免受DSS诱导的结肠炎。我们的数据表明，PKCι通过控制TFF 3表达促进肠上皮伤口愈合来减少DSS诱导的损伤。
The integrity of the intestinal epithelium is critical for the absorption and retention of fluid and nutrients. The intestinal epithelium also provides a barrier between the intestinal bacteria and the body's immune surveillance. Therefore, intestinal epithelial barrier function is critically important, and disruption of the intestinal epithelium results in rapid repair of the damaged area. We evaluated the requirement for protein kinase C iota (PKCι) in intestinal epithelial homeostasis and response to epithelial damage using a well-characterized mouse model of colitis. Mice were analyzed for the clinical, histological and cellular effects of dextran sodium sulfate (DSS) treatment. Knock out of the mouse PKCι gene (Prkci) in the intestinal epithelium (Prkci KO mice) had no effect on normal colonic homeostasis, however, Prkci KO mice were significantly more sensitive to DSS-induced colitis and death. After withdrawal of DSS, Prkci KO mice exhibited a continued increase in apoptosis, inflammation and damage to the intestinal microvasculature, and a progressive loss of trefoil factor 3 (TFF3) expression, a regulatory peptide important for intestinal wound healing. Knockdown of PKCι expression in HT-29 cells reduced wound healing and TFF3 expression, while addition of exogenous TFF3 restored wound healing in PKCι-depleted cells. Expression of PKCι in the intestinal epithelium protects against DSS-induced colitis. Our data suggest that PKCι reduces DSS-induced damage by promoting intestinal epithelial wound healing through the control of TFF3 expression.
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影响因子：
6.4
作者：
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通讯作者：
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