Long Non-Coding RNA MALAT1 Promotes Proliferation, Angiogenesis, and Immunosuppressive Properties of Mesenchymal Stem Cells by Inducing VEGF and IDO
Long Non-Coding RNA MALAT1 Promotes Proliferation, Angiogenesis, and Immunosuppressive Properties of Mesenchymal Stem Cells by Inducing VEGF and IDO
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长非编码 RNA MALAT1 通过诱导 VEGF 和 IDO 促进间充质干细胞的增殖、血管生成和免疫抑制特性。
DOI：
10.1002/jcb.25927
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发表时间：
2017-09-01
影响因子：
4
通讯作者：
Zhao, Guangfeng
中科院分区：
文献类型：
--
作者：
Li, Xiujun;Song, Yuxian;Zhao, Guangfeng
间充质干细胞在调节血管生成和免疫平衡方面发挥着重要作用。报道了子痫前期(PE)患者母胎界面间充质干细胞(MSCs)增殖和功能异常。MALAT1是已知的调控滋养层细胞功能的非编码长链RNA。然而，目前尚不清楚MALAT1是否调节MSCs与PE相关。在本研究中，我们发现重度PE患者脐带组织和间充质干细胞中MALAT1的表达均显著降低。MALAT1不影响MSCs的表型和分化。值得注意的是，将MALAT1质粒导入MSCs后，细胞周期进入G2/M期，并抑制细胞凋亡。MALAT1过表达的MSCs培养上清液可促进MSCs迁移、HTR-8/SVneo侵袭和HUVEC的管状形成，而si-MALAT1则相反。此外，我们还发现MALAT1诱导的血管内皮生长因子介导了MALAT1对MSCs的这些作用。此外，我们还发现MALAT1过表达的MSCs促进了M2巨噬细胞的极化，这种作用是由MALAT1诱导的IDO表达介导的，提示MALAT1可能在体内增强了MSCs的免疫抑制特性。此外，我们还研究了抑制MALAT1在PE中表达的因素，发现过氧化是MALAT1表达下调的原因之一。综上所述，我们的数据表明MALAT1在MSCs的增殖、血管生成和免疫抑制特性中是一个重要的内源性调节因子，提示它可能参与了PE的发病机制。(C)2017威利期刊公司。
Mesenchymal stem cells (MSCs) play an important role in regulating angiogenesis and immune balance. The abnormal MSCs in proliferation and function were reported at maternal fetal interface in patients with pre-eclampsia (PE). Long non-coding RNA MALAT1 was known to regulate the function of trophoblast cells. However, it is not clear whether MALAT1 regulates MSCs to be related to PE. In the present study, we found that the expression of MALAT1 was significantly reduced in both umbilical cord tissues and MSCs in patients with severe PE. MALAT1 did not affect the phenotype and differentiation of MSCs. Of note, transfection with MALAT1 plasmid into MSCs drove the cell cycle into G2/M phase and inhibited cell apoptosis. The supernatants from MALAT1-overexpressed MSCs promoted the migration of MSCs, invasion of HTR-8/SVneo and tube formation of HUVEC, while si-MALAT1 had the opposite effects. Moreover, we found that MALAT1-induced VEGF mediated these effects of MALAT1 on MSCs. Furthermore, we found that MALAT1-overexpressed MSCs promoted M2 macrophage polarization and this effect was mediated by MALAT1-induced IDO expression, suggesting that MALAT1 may enhance the immunosuppressive properties of MSCs in vivo. In addition, we also investigated the factors that inhibit MALAT1 expression in PE and found that peroxide was a cause for MALAT1 downregulation. Taken together, our data demonstrate that MALAT1 is an important endogenous regulator in the proliferation, angiogenesis, and immunosuppressive properties of MSCs, suggesting it may be involved in the pathogenesis of PE. (c) 2017 Wiley Periodicals, Inc.