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HIF1A/miR-20a-5p/TGFβ1 轴通过旁分泌方式调节脂肪来源干细胞,从而影响人真皮微血管内皮细胞的血管生成。

HIF1A/miR-20a-5p/TGFβ1 axis modulates adipose-derived stem cells in a paracrine manner to affect the angiogenesis of human dermal microvascular endothelial cells.

机构信息

Department of Plastic Surgery and Burns Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

J Cell Physiol. 2020 Mar;235(3):2091-2101. doi: 10.1002/jcp.29111. Epub 2019 Aug 1.

Abstract

Angiogenic cytokines secreted by the adipose-derived stem cells (ADSCs) might promote the angiogenesis of endothelial cells. In the present study, we hypothesize that miR-20a targets TGFB1 to modulate the transforming growth factor β1 (TGFβ1) secretion by ADSCs, therefore affecting the angiogenesis. We found that hypoxia-inducible factor 1A (HIF1A) and TGFβ1 expressions were increased by hypoxia, accompanied with promoted ADSC cell viability. Incubation with conditioned medium from ADSCs treated with hypoxia significantly enhanced the angiogenesis capacity of human dermal microvascular endothelial cells (HDMECs), while TGFB1-silenced ADSCs medium significantly reverses HDMECs angiogenesis. miR-20a suppresses the expression of TGFB1 and secretion of TGFβ1 by ADSCs via binding to its 3'untranslated region, therefore modulating the HDMEC angiogenesis via affecting the paracrine from ADSCs; the effects of miR-20a-overexpressed conditioned medium on HDMEC angiogenesis were significantly reversed by TGFB1-overexpressed conditioned medium. Finally, HIF1A suppressed the expression of miR-20a via targeting its promoter region, subsequently promoting the paracrine from ADSCs and HDMEC angiogenesis.

摘要

脂肪来源干细胞(ADSCs)分泌的血管生成细胞因子可能促进内皮细胞的血管生成。在本研究中,我们假设 miR-20a 通过靶向 TGFB1 来调节 ADSC 分泌的转化生长因子β1(TGFβ1),从而影响血管生成。我们发现,缺氧诱导因子 1A(HIF1A)和 TGFβ1 的表达在缺氧时增加,伴随着 ADSC 细胞活力的增强。用缺氧处理的 ADSC 条件培养基孵育可显著增强人真皮微血管内皮细胞(HDMEC)的血管生成能力,而沉默 TGFB1 的 ADSC 条件培养基可显著逆转 HDMEC 的血管生成。miR-20a 通过结合其 3'非翻译区来抑制 ADSC 中 TGFB1 的表达和 TGFβ1 的分泌,从而通过影响 ADSC 的旁分泌来调节 HDMEC 的血管生成;过表达 miR-20a 的条件培养基对 HDMEC 血管生成的作用可被过表达 TGFB1 的条件培养基显著逆转。最后,HIF1A 通过靶向其启动子区域抑制 miR-20a 的表达,从而促进 ADSC 和 HDMEC 的旁分泌和血管生成。

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