Survival of hypoxic human mesenchymal stem cells is enhanced by a positive feedback loop involving miR-210 and hypoxia-inducible factor 1

J Vet Sci. 2013;14(1):69-76. doi: 10.4142/jvs.2013.14.1.69. Epub 2013 Feb 5.

Abstract

The use of mesenchymal stem cells (MSCs) has emerged as a potential new treatment for myocardial infarction. However, the poor viability of MSCs after transplantation critically limits the efficacy of this new strategy. The expression of microRNA-210 (miR-210) is induced by hypoxia and is important for cell survival under hypoxic conditions. Hypoxia increases the levels of hypoxia inducible factor-1 (HIF-1) protein and miR-210 in human MSCs (hMSCs). miR-210 positively regulates HIF-1α activity. Furthermore, miR-210 expression is also induced by hypoxia through the regulation of HIF-1α. To investigate the effect of miR-210 on hMSC survival under hypoxic conditions, survival rates along with signaling related to cell survival were evaluated in hMSCs over-expressing miR-210 or ones that lacked HIF-1α expression. Elevated miR-210 expression increased survival rates along with Akt and ERK activity in hMSCs with hypoxia. These data demonstrated that a positive feedback loop involving miR-210 and HIF-1α was important for MSC survival under hypoxic conditions.

Keywords: cell survival; human mesenchymal stem cells; hypoxia; hypoxia inducible factor-1; microRNA-210.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival
  • Cobalt
  • Gene Expression Regulation / physiology*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / physiology*
  • MicroRNAs / metabolism*
  • Oxygen / pharmacology
  • Oxygen Consumption*
  • RNA, Small Interfering / metabolism

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN210 microRNA, human
  • MicroRNAs
  • RNA, Small Interfering
  • Cobalt
  • cobaltous chloride
  • Oxygen