The expression and role of miR-301a in human umbilical cord-derived mesenchymal stromal cells

Cytotherapy. 2013 Dec;15(12):1511-6. doi: 10.1016/j.jcyt.2013.06.007. Epub 2013 Sep 10.

Abstract

Background aims: Toll-like receptors (TLRs) are expressed in human umbilical cord-derived mesenchymal stromal cells (UC-MSCs), and activation of TLRs plays an important role in proliferation, differentiation and immunoregulatory activity of UC-MSCs. We investigated whether TLRs regulated the expression of microRNAs (miRNAs) in UC-MSCs and the role of miRNAs.

Methods and results: With miRNA microarray analysis, we demonstrated that the expression of many miRNAs varied when UC-MSCs were stimulated with the ligand of toll-like receptor 4 (TLR4), lipopolysaccharide (LPS). The expression of some miRNAs was verified by polymerase chain reaction. It was found that microRNA-301a (miR-301a) was up-regulated by the ligands of TLR3 and TLR4, LPS and polyinosinic acid:polycytidylic acid poly(I:C). However, the inhibitors of nuclear factor κB NF-κB and interferon regulatory factor 3 IRF3 signal attenuated the effect of LPS and poly(I:C) on miR-301a expression. Over-expression or lower expression of miR-301a affected the cytokine secretion of UC-MSCs.

Conclusions: The expression of miR-301a in UC-MSCs was regulated by TLRs, and miR-301a affected the cytokine secretion of UC-MSCs.

Keywords: IRF3; NF-κB; Toll-like receptors; mesenchymal stromal cells; miR-301a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Gene Expression Regulation, Developmental / drug effects
  • Humans
  • Interferon Regulatory Factor-3 / metabolism
  • Lipopolysaccharides / pharmacology
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • MicroRNAs / genetics*
  • NF-kappa B / genetics
  • Toll-Like Receptor 3 / biosynthesis*
  • Toll-Like Receptor 4 / biosynthesis*
  • Umbilical Cord / cytology*
  • Umbilical Cord / metabolism

Substances

  • IRF3 protein, human
  • Interferon Regulatory Factor-3
  • Lipopolysaccharides
  • MIRN301A microRNA, human
  • MicroRNAs
  • NF-kappa B
  • TLR3 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 3
  • Toll-Like Receptor 4