Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVβ5 receptor
Irisin reverses intestinal epithelial barrier dysfunction during intestinal injury via binding to the integrin αVβ5 receptor
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鸢尾素通过与整合素 α V β 5 受体结合逆转肠道损伤期间肠上皮屏障功能障碍
DOI：
10.1111/jcmm.14811
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发表时间：
2019-11-07
影响因子：
5.3
通讯作者：
Wu, Rongqian
中科院分区：
文献类型：
--
作者：
Bi, Jianbin;Zhang, Jia;Wu, Rongqian
如果没有特殊的治疗方法，肠道屏障的破坏会导致严重的临床结果。代谢紊乱和肠上皮细胞破坏在肠道屏障功能障碍中发挥着关键作用。鸢尾素是一种新发现的调节能量代谢的运动激素。然而，鸢尾素对肠道屏障功能的影响仍不清楚。在肠道缺血再灌注（IR）中评估了鸢尾素对肠道屏障功能障碍的治疗效果。在 Caco-2 细胞中研究了鸢尾素对肠道屏障功能的直接影响。在这里，我们发现肠道 IR 期间血清和肠道鸢尾素水平降低，并且外源性鸢尾素治疗可恢复小鼠肠道 IR 后的肠道屏障功能。同时，鸢尾素可减少肠道 IR 后的氧化应激、钙内流和内质网 (ER) 应激。此外，鸢尾素可以保护线粒体功能并减少肠细胞凋亡。抗鸢尾素的中和抗体显着加重肠道IR后的肠道损伤、氧化应激和肠细胞凋亡。进一步的研究表明，鸢尾素通过与整合素 α V β 5 受体结合激活 AMPK-UCP 2 通路。抑制整合素 α V β 5、AMPK 或 UCP 2 消除了鸢尾素在肠道屏障功能中的保护作用。总之，外源性鸢尾素通过整合素 α V β 5-AMPK-UCP 2 途径恢复肠道 IR 后的肠道屏障功能。
Disruption of the gut barrier results in severe clinical outcomes with no specific treatment. Metabolic disorders and destruction of enterocytes play key roles in gut barrier dysfunction. Irisin is a newly identified exercise hormone that regulates energy metabolism. However, the effect of irisin on gut barrier function remains unknown. The therapeutic effect of irisin on gut barrier dysfunction was evaluated in gut ischemia reperfusion (IR). The direct effect of irisin on gut barrier function was studied in Caco-2 cells. Here, we discovered that serum and gut irisin levels were decreased during gut IR and that treatment with exogenous irisin restored gut barrier function after gut IR in mice. Meanwhile, irisin decreased oxidative stress, calcium influx and endoplasmic reticulum (ER) stress after gut IR. Moreover, irisin protected mitochondrial function and reduced enterocyte apoptosis. The neutralizing antibody against irisin significantly aggravated gut injury, oxidative stress and enterocyte apoptosis after gut IR. Further studies revealed that irisin activated the AMPK-UCP 2 pathway via binding to the integrin alpha V beta 5 receptor. Inhibition of integrin alpha V beta 5, AMPK or UCP 2 abolished the protective role of irisin in gut barrier function. In conclusion, exogenous irisin restores gut barrier function after gut IR via the integrin alpha V beta 5-AMPK-UCP 2 pathway.