Activating AMPK to Restore Tight Junction Assembly in Intestinal Epithelium and to Attenuate Experimental Colitis by Metformin.
Activating AMPK to Restore Tight Junction Assembly in Intestinal Epithelium and to Attenuate Experimental Colitis by Metformin.
复制标题
二甲双胍激活 AMPK 恢复肠上皮的紧密连接组装并减轻实验性结肠炎
DOI：
10.3389/fphar.2018.00761
复制
发表时间：
2018
影响因子：
5.6
通讯作者：
Xu Q
中科院分区：
文献类型：
--
作者：
Chen L;Wang J;You Q;He S;Meng Q;Gao J;Wu X;Shen Y;Sun Y;Wu X;Xu Q
腺苷单磷酸活化蛋白激酶（AMPK）是能量代谢的关键分子，最近被报道在肠上皮分化和屏障功能中发挥潜在作用；然而，其在炎症性肠病病理过程中的作用和机制尚不清楚。在本研究中，我们发现在葡聚糖硫酸钠诱导的实验性结肠炎的发生和发展过程中，结肠组织中AMPK的磷酸化与疾病的严重程度呈负相关。二甲双胍激活AMPK可显著控制结肠炎的进展，这与小鼠结肠上皮紧密连接的维持有关。此外，我们在结肠上皮Caco2细胞中的体外数据显示，二甲双胍通过ampk依赖的方式促进紧密连接的表达和组装。总的来说，我们的结果表明，通过临床上安全的药物二甲双胍激活AMPK可能是治疗结肠炎的有益选择。
Adenosine monophosphate-activated protein kinase (AMPK), a crucial molecule in energy metabolism, is reported to play a potential role in gut epithelial differentiation and barrier function recently; however, its performance and mechanisms in the pathological process of inflammatory bowel diseases remain unidentified. In this study, we have found that the phosphorylation of AMPK in colonic tissues is negatively correlated with severity of disease during the initiation and development of experimental colitis induced by dextran sulfate sodium. Activation of AMPK by metformin significantly controls the progression of colitis, which is associated with the maintenance of tight junction in colonic epithelium in mice. Moreover, our in vitro data in colonic epithelial Caco2 cells shows that metformin promotes expression and assembly of tight junctions via an AMPK-dependent way. Overall, our results suggested that activating AMPK by a clinically safe drug metformin could be a beneficial choice for colitis treatment.
登录
查看更多内容
影响因子：
4
作者：
Calder, Michele D.;Edwards, Nicole A.;Watson, Andrew J.
通讯作者：
Watson, Andrew J.
影响因子：
4.2
作者：
Frieri, Giuseppe;Galletti, Brigida;Viscido, Angelo
通讯作者：
Viscido, Angelo
影响因子：
4.4
作者：
Satyam, Abhigyan;Kannan, Lakshmi;Tsokos, George C.
通讯作者：
Tsokos, George C.
影响因子：
4.1
作者：
Koh, Seong-Joon;Kim, Jung Mogg;Kim, Joo Sung
通讯作者：
Kim, Joo Sung
AMPK：代谢和线粒体稳态的监护人。
DOI：
10.1038/nrm.2017.95
发表时间：
2018-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Herzig S;Shaw RJ
通讯作者：
Shaw RJ