Protein kinase CK2 is a critical regulator of epithelial homeostasis in chronic intestinal inflammation.

Protein kinase CK2 is a critical regulator of epithelial homeostasis in chronic intestinal inflammation.
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DOI:
10.1038/mi.2012.57
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发表时间:
2013-01
期刊:
影响因子:
8
通讯作者:
--
中科院分区:
医学1区
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--
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在结肠炎期间恢复肠上皮内稳态的分子机制尚未完全了解。在这里,我们报告说,在肠道炎症,多种炎性细胞因子促进细胞增殖和凋亡,丝氨酸/苏氨酸激酶CK 2的主调节活性。在慢性结肠炎动物模型中观察到粘膜CK 2蛋白表达和活性增强,特别是在肠上皮细胞内。用细胞因子体外处理肠上皮细胞系导致CK 2表达增加及其催化α亚基的核转位。同样,CK 2 α的核转位是在溃疡性结肠炎和克罗恩病患者的结肠隐窝中观察到的显著特征。进一步的体外研究表明,CK 2活性促进上皮恢复,并保护正常肠上皮细胞免受苦参碱诱导的凋亡。这些观察结果将CK 2鉴定为肠上皮细胞的稳态特性的关键调节剂,其部分地通过在炎症条件下抑制细胞凋亡来促进伤口愈合。
Molecular mechanisms that restore intestinal epithelial homeostasis during colitis are incompletely understood. Here, we report that during intestinal inflammation, multiple inflammatory cytokines promote the activity of a master regulator of cell proliferation and apoptosis, serine/threonine kinase CK2. Enhanced mucosal CK2 protein expression and activity were observed in animal models of chronic colitis, particularly within intestinal epithelial cells. In-vitro treatment of intestinal epithelial cell lines with cytokines resulted in increased CK2 expression and nuclear translocation of its catalytic α subunit. Similarly, nuclear translocation of CK2α was a prominent feature observed in colonic crypts from individuals with ulcerative colitis and Crohn's disease. Further invitro studies revealed that CK2 activity promotes epithelial restitution, and protects normal intestinal epithelial cells from cytokine-induced apoptosis. These observations identify CK2 as a key regulator of homeostatic properties of the intestinal epithelium that serves to promote wound healing, in part through inhibition of apoptosis under conditions of inflammation.
DOI: 10.1007/s00018-009-9153-z
发表时间: 2009-06
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