MicroRNA-150 regulates mobilization and migration of bone marrow-derived mononuclear cells by targeting Cxcr4

Research output: Contribution to journalArticle

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Abstract

The interaction between chemokine receptor type 4 (CXCR4) and its ligand, stromal cell-derived factor (SDF)-1, plays an important role in stem cell mobilization and migration in ischemic tissues. MicroRNAs (miRs) are key regulators of stem cell function and are involved in regulation of stem cell survival and differentiation to adopt different cell lineages. In this study, we show that ischemia inhibits the expression of miR-150 in BM-derived mononuclear cells (MNC) and activates its target Cxcr4 gene. Our results show that miR-150/CXCR4 cascade enhances MNC mobilization and migration. By using mouse acute myocardial infarction (MI) model, we found that MNCs in peripheral blood (PB) were increased significantly at day 5 after AMI as compared to control group and the number of CXCR4 positive MNCs both in bone marrow (BM) and PB was also markedly increased after MI. Analysis by microarray-based miRNA profiling and real-time PCR revealed that the expression of miR-150 which targets Cxcr4 gene as predicted was significantly downregulated in BM-MNCs after MI. Abrogation of miR-150 markedly increased CXCR4 protein expression suggesting its target gene. To show that miR-150 regulates MNC mobilization, knockdown of miR-150 in BM-MNCs by specific antisense inhibitor resulted in their higher migration ability in vitro as compared to scramble-transfected MNCs. Furthermore, in vivo BM transplantation of MNCs lacking miR-150 expression by lentiviral vector into the irradiated wild type mice resulted in the increased number of MNCs in PB after AMI as compared to control. In conclusion, this study demonstrates that ischemia mobilizes BM stem cells via miR-150/CXCR4 dependent mechanism and miR-150 may be a novel therapeutic target for stem cell migration to the ischemic tissue for neovascularization and repair.

Original languageEnglish (US)
Article numbere23114
JournalPloS one
Volume6
Issue number10
DOIs
StatePublished - Nov 2 2011
Externally publishedYes

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MicroRNAs
microRNA
bone marrow
stem cells
Stem cells
Bone
Stem Cells
Bone Marrow
myocardial infarction
Cell Movement
Myocardial Infarction
ischemia
Blood
Ischemia
Genes
cells
Hematopoietic Stem Cell Mobilization
blood
Chemokine CXCL12
Chemokine Receptors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

MicroRNA-150 regulates mobilization and migration of bone marrow-derived mononuclear cells by targeting Cxcr4. / Tano, Nobuko; Kim, Ha Won; Ashraf, Muhammad.

In: PloS one, Vol. 6, No. 10, e23114, 02.11.2011.

Research output: Contribution to journalArticle

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