Connexin 43-Mediated Mitochondrial Transfer of iPSC-MSCs Alleviates Asthma Inflammation.
Connexin 43-Mediated Mitochondrial Transfer of iPSC-MSCs Alleviates Asthma Inflammation.
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Connexin 43 介导的 iPSC-MSC 线粒体转移可减轻哮喘炎症
DOI：
10.1016/j.stemcr.2018.09.012
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发表时间：
2018-11-13
影响因子：
5.9
通讯作者：
Fu QL
中科院分区：
文献类型：
--
作者：
Yao Y;Fan XL;Jiang D;Zhang Y;Li X;Xu ZB;Fang SB;Chiu S;Tse HF;Lian Q;Fu QL
我们之前确定了人诱导多能干细胞 (iPSC) 衍生的间充质干细胞 (MSC) 在哮喘炎症中的免疫调节作用。线粒体从骨髓间充质干细胞转移到上皮细胞可以减轻小鼠的急性肺损伤。然而，线粒体从 iPSC-MSC 转移到哮喘上皮细胞的影响以及这些影响的机制尚不清楚。我们发现 iPSC-MSC 移植显着减少了 T 辅助细胞 2 细胞因子，减轻了上皮细胞的线粒体功能障碍，并减轻了小鼠的哮喘炎症。 iPSC-MSC 和上皮细胞之间形成隧道纳米管 (TNT)，在体外和小鼠体内均观察到线粒体通过 TNT 从 iPSC-MSC 转移到上皮细胞。 iPSC-MSC 中连接蛋白 43 (CX43) 的过度表达或沉默表明，CX43 通过介导 iPSC-MSC 和上皮细胞之间的线粒体转移，在调节 TNT 形成中发挥关键作用。这项研究提供了针对哮喘炎症的治疗策略。 iPSC-MSC 减轻哮喘炎症并保护上皮细胞 iPSC-MSC 的保护归因于通过 TNT 进行线粒体转移 CX43 介导的 TNT 形成调节 iPSC-MSC 的线粒体捐赠。在这篇文章中，Fu、Lian 及其同事表明，源自人类诱导多能干细胞的间充质干细胞可以转移其线粒体来拯救受损的支气管上皮细胞，从而减轻哮喘炎症。连接蛋白 43 是间隙连接的组成部分，通过调节细胞间隧道纳米管的形成，在线粒体转移过程中发挥着关键作用。
We previously identified an immunomodulatory role of human induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (MSCs) in asthmatic inflammation. Mitochondrial transfer from bone marrow MSCs to epithelial cells can result in the attenuation of acute lung injury in mice. However, the effects of mitochondrial transfer from iPSC-MSCs to epithelial cells in asthma and the mechanisms underlying these effects are unclear. We found that iPSC-MSC transplantation significantly reduced T helper 2 cytokines, attenuated the mitochondrial dysfunction of epithelial cells, and alleviated asthma inflammation in mice. Tunneling nanotubes (TNTs) were formed between iPSC-MSCs and epithelial cells, and mitochondrial transfer from iPSC-MSCs to epithelial cells via TNTs was observed both in vitro and in mice. Overexpression or silencing of connexin 43 (CX43) in iPSC-MSCs demonstrated that CX43 plays a critical role in the regulation of TNT formation by mediating mitochondrial transfer between iPSC-MSCs and epithelial cells. This study provides a therapeutic strategy for targeting asthma inflammation. iPSC-MSCs attenuate asthma inflammation and protect epithelial cells The protection of iPSC-MSCs is attributable to mitochondrial transfer via TNTs CX43-mediated TNT formation regulates the mitochondrial donation of iPSC-MSCs In this article, Fu, Lian, and colleagues show that mesenchymal stem cells derived from human induced pluripotent stem cells can transfer their mitochondria to rescue the injured bronchial epithelial cells, which attenuates asthma inflammation. Connexin 43, a component of gap junctions, plays a critical role during the process of mitochondrial transfer by regulating intercellular tunneling nanotube formation.
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影响因子：
5.6
作者：
Cao, Ju;Wong, Chun K.;Lam, Christopher W. K.
通讯作者：
Lam, Christopher W. K.
DOI：
10.1165/rcmb.2013-0519oc
发表时间：
2015-01-01
影响因子：
6.4
作者：
Jaffer, Omar A.;Carter, A. Brent;Anderson, Mark E.
通讯作者：
Anderson, Mark E.
影响因子：
3.1
作者：
Crisostomo, Paul R.;Wang, Meijing;Meldrum, Daniel R.
通讯作者：
Meldrum, Daniel R.
源自人类诱导多能干细胞的间充质干细胞调节过敏性鼻炎的 T 细胞表型
影响因子：
12.4
作者：
Fu, Q. L.;Chow, Y. Y.;Xu, G.
通讯作者：
Xu, G.
DOI：
10.1165/ajrcmb.26.5.4489
发表时间：
2002-05-01
影响因子：
6.4
作者：
Plotkowski, MC;Póvoa, HCC;Puchelle, E
通讯作者：
Puchelle, E