Hypoxia Promotes Vascular Smooth Muscle Cell (VSMC) Differentiation of Adipose-Derived Stem Cell (ADSC) by Regulating Mettl3 and Paracrine Factors
Hypoxia Promotes Vascular Smooth Muscle Cell (VSMC) Differentiation of Adipose-Derived Stem Cell (ADSC) by Regulating Mettl3 and Paracrine Factors
复制标题
缺氧通过调节Mettl3和旁分泌因子促进血管平滑肌细胞（VSMC）分化为脂肪干细胞（ADSC）
DOI：
10.1155/2020/2830565
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发表时间：
2020-02-20
影响因子：
4.3
通讯作者：
Kuang, Yanping
中科院分区：
文献类型：
--
作者：
Lin, Jiaying;Zhu, Qianqian;Kuang, Yanping
脂肪干细胞（ADSC）是一种替代性且侵入性较小的间充质干细胞来源，可用于开发组织再生的生物治疗策略，其治疗应用取决于对其生理特征的了解。 N6-甲基腺苷 (m6A) 是最常见的 mRNA 化学修饰，最近被发现在细胞谱系分化和发育中发挥重要作用。然而，m6A 修饰在 ADSC 血管平滑肌细胞 (VSMC) 分化中的作用仍不清楚。在此，我们研究了 N6-腺苷甲基转移酶 (Mettl3) 和去甲基酶 (Fto 和 Alkbh5) 的表达，发现 Mettl3 在经历血管平滑肌分化诱导的 ADSC 中上调。此外，Mettle3的沉默降低了VSMC特异性标记物的表达水平，包括α-SMA、SM22α、钙调蛋白和SM-MHC。同时，Mettl3敲低还降低了旁分泌因子的表达，包括VEGF、HGF、TGF-β、GM-CSF、bFGF和SDF-1。此外，我们的结果表明，缺氧应激促进ADSC分化为VMSCs，并通过介导Mettl3基因表达来调节VEGF、HGF、TGF-β、GM-CSF、bFGF和SDF-1的分泌。这些观察结果可能有助于理解表观转录组调控在 ADSC 的 VSMC 分化中的作用，并为组织再生的新治疗策略提供有前景的前景。
Adipose-derived stem cell (ADSC) is an alternative and less invasive source of mesenchymal stem cells which can be used to develop biological treatment strategies for tissue regeneration, and their therapeutic applications hinge on an understanding of their physiological characteristics. N6-Methyladenosine (m6A) is the most common chemical modification of mRNAs and has recently been revealed to play important roles in cell lineage differentiation and development. However, the role of m6A modification in the vascular smooth muscle cell (VSMC) differentiation of ADSCs remains unclear. Herein, we investigated the expression of N6-adenosine methyltransferases (Mettl3) and demethylases (Fto and Alkbh5) and found that Mettl3 was upregulated in ADSCs undergoing vascular smooth muscle differentiation induction. Moreover, silence of Mettle3 reduced the expression level of VSMC-specific markers, including α-SMA, SM22α, calponin, and SM-MHC. Meanwhile, Mettl3 knockdown also decreased the expression of paracrine factors, including VEGF, HGF, TGF-β, GM-CSF, bFGF, and SDF-1. In addition, our results suggested that hypoxia stress promotes the ADSC differentiate into VMSCs and regulates the secretion of VEGF, HGF, TGF-β, GM-CSF, bFGF, and SDF-1 by mediating Mettl3 gene expression. These observations might contribute to novel progress in understanding the role of epitranscriptomic regulation in the VSMC differentiation of ADSCs and provide a promising perspective for new therapeutic strategies for tissue regeneration.