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miR-21 Modulates the Immunoregulatory Function of Bone Marrow Mesenchymal Stem Cells Through the PTEN/Akt/TGF-β1

Tingting Wu1, Yi Liu2, Zhipeng Fan3

  • 1Molecular Laboratory for Gene Therapy and Tooth Regeneration.

Stem Cells (Dayton, Ohio)
|June 19, 2015
PubMed

Insights

MicroRNA-21 (miR-21) suppresses the immune function of mesenchymal stem cells (MSCs) by inhibiting transforming growth factor-β1 (TGF-β1). Deleting miR-21 enhances MSCs

Area of Science:

  • Immunology
  • Stem Cell Biology
  • Molecular Biology

Background:

  • Mesenchymal stem cells (MSCs) possess immunomodulatory properties.
  • The role of microRNAs (miRNAs) in regulating MSC immunomodulation is not fully understood.
  • MicroRNA-21 (miR-21) is implicated in stem cell functions but its effect on MSC immunomodulation is unclear.

Purpose of the Study:

  • To investigate the role of miR-21 in modulating the immunoregulatory function of MSCs.
  • To elucidate the molecular mechanism by which miR-21 affects MSC immunomodulation.
  • To assess the therapeutic potential of miR-21-deficient MSCs in an inflammatory disease model.

Main Methods:

  • Utilized miR-21 knockout (miR-21(-/-)) and wild-type (WT) bone marrow MSCs (BMMSCs).
  • Assessed TGF-β1 secretion, regulatory T cell induction, and downstream signaling pathways (PTEN, Akt, NF-κB).
  • Evaluated the efficacy of miR-21(-/-) BMMSCs in a mouse model of experimental colitis.

Main Results:

  • miR-21(-/-) BMMSCs exhibited enhanced immunosuppressive function compared to WT BMMSCs.
  • miR-21(-/-) BMMSCs secreted more TGF-β1, leading to increased CD4(+) Foxp3(+) regulatory T cell induction.
  • miR-21 targets PTEN, inhibiting the TGF-β1 pathway and consequently suppressing Akt and NF-κB activation.
  • Adoptive transfer of miR-21(-/-) BMMSCs ameliorated experimental colitis in a TGF-β1-dependent manner.

Conclusions:

  • miR-21 negatively regulates the immunoregulatory function of MSCs by inhibiting TGF-β1.
  • The miR-21/PTEN/TGF-β1 axis is a key mechanism controlling MSC immunomodulation.
  • miR-21-deficient MSCs represent a potential cell-based therapy for inflammatory diseases.
Keywords:
ImmunoregulationMesenchymal stem cellsPTENTransforming growth factor-β1miR-21

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