ACF7 regulates inflammatory colitis and intestinal wound response by orchestrating tight junction dynamics.
ACF7 regulates inflammatory colitis and intestinal wound response by orchestrating tight junction dynamics.
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ACF7 通过协调紧密连接动力学来调节炎症性结肠炎和肠道伤口反应
DOI：
10.1038/ncomms15375
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发表时间：
2017-05-25
影响因子：
16.6
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Ma Y;Yue J;Zhang Y;Shi C;Odenwald M;Liang WG;Wei Q;Goel A;Gou X;Zhang J;Chen SY;Tang WJ;Turner JR;Yang F;Liang H;Qin H;Wu X
在肠上皮中，细胞/细胞连接的异常调节导致肠屏障功能障碍，从而促进炎症性肠病(IBD)的发生和加重。然而，目前尚不清楚细胞骨架网络的协调行为如何有助于细胞连接动力学。在这份报告中，我们确定了ACF7，一种微管和F-肌动蛋白的交联剂，在这一过程中发挥了重要作用。在体外，ACF7的丢失会导致微管组织的异常，紧密连接的稳定，并损害伤口的闭合。用小鼠遗传学的方法，我们发现ACF7的消融抑制了小鼠的肠道伤口愈合，并极大地增加了对实验性结肠炎的易感性。ACF7的水平也与人类患者溃疡性结肠炎(UC)的发生和发展有关。总之，我们的结果揭示了一个重要的分子机制，即在肠道创伤修复和IBD的发展过程中，协调的细胞骨架动力学有助于细胞黏附调节。
In the intestinal epithelium, the aberrant regulation of cell/cell junctions leads to intestinal barrier defects, which may promote the onset and enhance the severity of inflammatory bowel disease (IBD). However, it remains unclear how the coordinated behaviour of cytoskeletal network may contribute to cell junctional dynamics. In this report, we identified ACF7, a crosslinker of microtubules and F-actin, as an essential player in this process. Loss ofACF7leads to aberrant microtubule organization, tight junction stabilization and impaired wound closurein vitro. With the mouse genetics approach, we show that ablation ofACF7inhibits intestinal wound healing and greatly increases susceptibility to experimental colitis in mice.ACF7level is also correlated with development and progression of ulcerative colitis (UC) in human patients. Together, our results reveal an important molecular mechanism whereby coordinated cytoskeletal dynamics contributes to cell adhesion regulation during intestinal wound repair and the development of IBD.