MicroRNA-195a-3p inhibits angiogenesis by targeting Mmp2 in murine mesenchymal stem cells

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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis

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Fan Gao1, Meng Sun2, Yumei Gong3

  • 1Department of Ophthalmology, Eye Institute of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.

Molecular Reproduction and Development
|March 19, 2016
PubMed

Insights

MicroRNA-195a-3p inhibits angiogenesis by reducing mesenchymal stem cell proliferation and migration. This microRNA, decreased in hypoxia, shows therapeutic potential as an angiogenesis inhibitor for conditions like choroidal neovascularization.

Area of Science:

  • Molecular Biology
  • Stem Cell Biology
  • Ophthalmology

Background:

  • MicroRNAs (miRNAs) regulate physiological and pathological processes, including angiogenesis.
  • Mesenchymal stem cells (MSCs) are recruited to neovascularization lesions.
  • The role of miRNA-195 in MSCs and angiogenesis is unknown.

Purpose of the Study:

  • To investigate the function of miR-195a-3p in mesenchymal stem cells (MSCs).
  • To determine the role of miR-195a-3p in regulating angiogenesis.
  • To evaluate the therapeutic potential of miR-195a-3p as an angiogenesis inhibitor.

Main Methods:

  • Assessed miR-195a-3p abundance in hypoxia-treated MSCs.
  • Overexpressed miR-195a-3p in MSCs to study effects on proliferation, migration, and anti-angiogenic factors.
  • Identified matrix metalloproteinase 2 (Mmp2) as a miR-195a-3p target.
  • Silenced Mmp2 to observe effects on MSCs.
  • Tested therapeutic potential in a laser-induced choroidal neovascularization mouse model.

Main Results:

  • miR-195a-3p abundance decreased in hypoxia-treated MSCs.
  • Overexpression of miR-195a-3p reduced MSC proliferation and migration.
  • miR-195a-3p overexpression increased pigment epithelium-derived factor (PEDF) activation.
  • Mmp2 was confirmed as a target of miR-195a-3p.
  • Silencing Mmp2 mimicked the reduced proliferation and migration observed with miR-195a-3p overexpression.
  • miR-195a-3p demonstrated therapeutic potential in a mouse model of choroidal neovascularization.

Conclusions:

  • miR-195a-3p acts as a negative modulator of angiogenesis.
  • miR-195a-3p inhibits MSC proliferation and migration, partly through targeting Mmp2.
  • miR-195a-3p holds potential as a therapeutic agent for inhibiting angiogenesis in diseases like choroidal neovascularization.

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