A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5-Mediated GDF6 Expression.
A Novel Human Long Noncoding RNA SCDAL Promotes Angiogenesis through SNF5-Mediated GDF6 Expression.
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新型人类长非编码 RNA SCDAL 通过 SNF5 介导的 GDF6 表达促进血管生成
DOI：
10.1002/advs.202004629
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Wang J
中科院分区：
文献类型：
--
作者：
Wu R;Hu W;Chen H;Wang Y;Li Q;Xiao C;Fan L;Zhong Z;Chen X;Lv K;Zhong S;Shi Y;Chen J;Zhu W;Zhang J;Hu X;Wang J
血管生成是血管发育的关键。调控长非编码RNA(LncRNAs)在介导血管生成中的作用尚不清楚。人胚胎干细胞来源的间充质干细胞(HES-MSCs)比人骨髓来源的MSCs(HBM-MSCs)具有更强的抗心肌缺血作用，并能促进新生血管的形成。本研究的目的是寻找在HES-MSCs中丰富的血管生成lncRNAs，并探讨其作用和机制。AC103746.1是在HES-MSCs和HBM-MSCs中检测到的基因间高表达的lncRNA之一，命名为SCDAL(干细胞衍生的血管生成lncRNA)。SCDAL基因敲除可显著降低HES-MSCs在心肌梗死后的血管生成潜能和修复作用，而SCDAL在HES-MSCs和HBM-MSCs中的过表达均可促进血管生成和心功能恢复。在机制上，SCDAL通过与GDF6启动子上的SNF5直接相互作用诱导生长分化因子6(GDF6)的表达。分泌型GDF6通过非典型的血管内皮生长因子受体2激活促进血管内皮细胞生成。此外，SCDAL-GDF6在人内皮细胞中表达，并在体外和体内直接促进内皮细胞血管生成。因此，这些发现揭示了一个先前未知的依赖于lncRNA的血管生成调控电路。靶向干预SCDAL-GDF6通路具有治疗缺血性心脏病的潜力。长非编码RNA(Long Non Coding RNA，LncRNA)SCDAL(干细胞衍生血管生成RNA)被认为是人胚胎干细胞来源的间充质干细胞(HES-MSCs)在缺血心脏中血管生成的重要调节因子。SCDAL通过招募SNF5到GDF6启动子来启动GDF6的表达。分泌型GDF6通过血管内皮生长因子受体2途径促进内皮血管生成。
Angiogenesis is essential for vascular development. The roles of regulatory long noncoding RNAs (lncRNAs) in mediating angiogenesis remain under‐explored. Human embryonic stem cell‐derived mesenchymal stem cells (hES‐MSCs) are shown to exert more potent cardioprotective effects against cardiac ischemia than human bone marrow‐derived MSCs (hBM‐MSCs), associated with enhanced neovascularization. The purpose of this study is to search for angiogenic lncRNAs enriched in hES‐MSCs, and investigate their roles and mechanisms. AC103746.1 is one of the most highly expressed intergenic lncRNAs detected in hES‐MSCs versus hBM‐MSCs, and named as SCDAL (stem cell‐derived angiogenic lncRNA). SCDAL knockdown significantly reduce the angiogenic potential and reparative effects of hES‐MSCs in the infarcted hearts, while overexpression of SCDAL in either hES‐MSCs or hBM‐MSCs exhibits augmented angiogenesis and cardiac function recovery. Mechanistically, SCDAL induces growth differentiation factor 6 (GDF6) expression via direct interaction with SNF5 at GDF6 promoter. Secreted GDF6 promotes endothelial angiogenesis via non‐canonical vascular endothelial growth factor receptor 2 activation. Furthermore, SCDAL‐GDF6 is expressed in human endothelial cells, and directly enhances endothelial angiogenesis in vitro and in vivo. Thus, these findings uncover a previously unknown lncRNA‐dependent regulatory circuit for angiogenesis. Targeted intervention of the SCDAL‐GDF6 pathway has potential as a therapy for ischemic heart diseases. Long noncoding RNA (lncRNA) SCDAL (stem cell‐derived angiogenic lncRNA) is identified as a critical regulator for angiogenic actions of human embryonic stem cell‐derived mesenchymal stem cells (hES‐MSCs) in ischemic hearts. SCDALinitiates growth differentiation factor 6 (GDF6) expression by recruiting SNF5 to GDF6 promoter. Secreted GDF6 promotes endothelial angiogenesis through vascular endothelial growth factor receptor 2 pathway.
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影响因子：
64.8
作者：
Konermann S;Brigham MD;Trevino AE;Joung J;Abudayyeh OO;Barcena C;Hsu PD;Habib N;Gootenberg JS;Nishimasu H;Nureki O;Zhang F
通讯作者：
Zhang F
DOI：
10.1093/bioinformatics/btr209
发表时间：
2011-07-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Lin MF;Jungreis I;Kellis M
通讯作者：
Kellis M
DOI：
10.4049/jimmunol.1501407
发表时间：
2015-10-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hong J;Persaud SP;Horvath S;Allen PM;Evavold BD;Zhu C
通讯作者：
Zhu C
DOI：
10.1073/pnas.0914318107
发表时间：
2010-02-09
影响因子：
11.1
作者：
Leppanen, Veli-Matti;Prota, Andrea E.;Alitalo, Kari
通讯作者：
Alitalo, Kari
影响因子：
4.8
作者：
Heiss, Maximilian;Hellstrom, Mats;Korff, Thomas
通讯作者：
Korff, Thomas