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

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.

Keywords: HIF1A; TGFβ1; human dermal microvascular endothelial cells; mesenchymal stem cells; miR-20a-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adipocytes / metabolism
  • Adipose Tissue / metabolism
  • Angiogenesis Inducing Agents / metabolism
  • Cell Survival / genetics
  • Cells, Cultured
  • Endothelial Cells / metabolism*
  • Humans
  • Hypoxia / genetics
  • Hypoxia / metabolism
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • MicroRNAs / metabolism*
  • Microvessels / metabolism*
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Physiologic
  • Promoter Regions, Genetic / genetics
  • Skin / metabolism*
  • Stem Cells / metabolism
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • 3' Untranslated Regions
  • Angiogenesis Inducing Agents
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN20a microRNA, human
  • MicroRNAs
  • TGFB1 protein, human
  • Transforming Growth Factor beta1