The miR-148/152 family contributes to angiogenesis of human pluripotent stem cell- derived endothelial cells by inhibiting MEOX2.
The miR-148/152 family contributes to angiogenesis of human pluripotent stem cell- derived endothelial cells by inhibiting MEOX2.
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DOI：
10.1016/j.omtn.2023.04.020
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发表时间：
2023-06-13
期刊：
影响因子：
--
通讯作者：
Hu, Shijun
中科院分区：
文献类型：
--
作者：
Ding, Fengyue;Wu, Hongchun;Han, Xinglong;Jiang, Xue;Xiao, Yang;Tu, Yuanyuan;Yu, Miao;Lei, Wei;Hu, Shijun
人多能干细胞来源的内皮细胞(hPSC-ECs)是心血管疾病机制研究、细胞治疗和药物筛选急需的人内皮细胞的重要来源。本研究旨在探讨由miR-148A、miR-148B和miR-152组成的miR-148/152家族在hPSC-ECs中的功能及其调控机制，为在上述应用中改善EC功能提供新的靶点。与野生型(WT)组相比，miR-148/152家族基因敲除(TKO)显著降低了人胚胎干细胞(HESCs)的内皮分化效率，削弱了其来源的内皮细胞(hESC-ECs)的增殖、迁移和毛细血管样管形成能力。过表达miR-152可部分恢复TKO hESC-ECs的血管生成能力。此外，间充质同源框2(MEOX2)被确认为miR-148/152家族的直接靶点。MEOX2基因敲除可部分恢复TKO hESC-ECs的血管生成能力。Matrigel Plug实验进一步表明，miR-148/152家族基因敲除后，hESC-ECs的体内血管生成能力受到抑制，而miR-152过表达则使其体内血管生成能力增强。因此，miR-148/152家族对维持hPSC-ECs的血管生成能力至关重要，可作为提高EC治疗的功能效益和促进内源性血管重建的靶点。Hu及其同事通过直接靶向间充质同源盒2(MEOX2)，在hPSC来源的内皮细胞中展示了miR-148/152家族的促血管生成功能，并揭示了miR-148/152家族在血管重建治疗中的巨大潜力。
Human pluripotent stem cell-derived endothelial cells (hPSC-ECs) represent a promising source of human ECs urgently needed for the study of cardiovascular disease mechanisms, cell therapy, and drug screening. This study aims to explore the function and regulatory mechanism of the miR-148/152 family consisting of miR-148a, miR-148b, and miR-152 in hPSC-ECs, so as to provide new targets for improving EC function during the above applications. In comparison with the wild-type (WT) group, miR-148/152 family knockout (TKO) significantly reduced the endothelial differentiation efficiency of human embryonic stem cells (hESCs), and impaired the proliferation, migration, and capillary-like tube formatting abilities of their derived ECs (hESC-ECs). Overexpression of miR-152 partially restored the angiogenic capacity of TKO hESC-ECs. Furthermore, the mesenchyme homeobox 2 (MEOX2) was validated as the direct target of miR-148/152 family. MEOX2 knockdown resulted in partial restoration of the angiogenesis ability of TKO hESC-ECs. The Matrigel plug assay further revealed that the in vivo angiogenic capacity of hESC-ECs was impaired by miR-148/152 family knockout, and increased by miR-152 overexpression. Thus, the miR-148/152 family is crucial for maintaining the angiogenesis ability of hPSC-ECs, and might be used as a target to enhance the functional benefit of EC therapy and promote endogenous revascularization. Hu and colleagues demonstrated a pro-angiogenic function of the miR-148/152 family in hPSC-derived ECs by directly targeting the mesenchyme homeobox 2 (MEOX2), and revealed a great potential of the miR-148/152 family in revascularization therapy.
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DOI：
10.1074/jbc.m113.495531
发表时间：
2014-02-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Di Bernardini E;Campagnolo P;Margariti A;Zampetaki A;Karamariti E;Hu Y;Xu Q
通讯作者：
Xu Q
影响因子：
9.8
作者：
Marziano C;Genet G;Hirschi KK
通讯作者：
Hirschi KK
影响因子：
13.6
作者：
Chiba, Takuto;Cerqueira, Debora M.;Sims-Lucas, Sunder
通讯作者：
Sims-Lucas, Sunder
影响因子：
5.6
作者：
Liu, Xing-Li;Wang, Gang;Lyu, Liang
通讯作者：
Lyu, Liang
影响因子：
20.1
作者：
Gu M;Nguyen PK;Lee AS;Xu D;Hu S;Plews JR;Han L;Huber BC;Lee WH;Gong Y;de Almeida PE;Lyons J;Ikeno F;Pacharinsak C;Connolly AJ;Gambhir SS;Robbins RC;Longaker MT;Wu JC
通讯作者：
Wu JC