| First Author | Wu T | Year | 2015 |
| Journal | Stem Cells | Volume | 33 |
| Issue | 11 | Pages | 3281-90 |
| PubMed ID | 26086742 | Mgi Jnum | J:228676 |
| Mgi Id | MGI:5708452 | Doi | 10.1002/stem.2081 |
| Citation | Wu T, et al. (2015) miR-21 Modulates the Immunoregulatory Function of Bone Marrow Mesenchymal Stem Cells Through the PTEN/Akt/TGF-beta1 Pathway. Stem Cells 33(11):3281-90 |
| abstractText | microRNAs (miRNAs) act as regulatory signals for maintaining stemness, self-renewal, and differentiation of mesenchymal stem cells (MSCs), but whether miRNAs modulate the immunoregulatory function of MSCs remains largely unknown. Here, we show that miR-21 negatively regulates the activity of immunoregulatory cytokine transforming growth factor-beta1 (TGF-beta1) in MSCs. Consistently, bone marrow MSCs (BMMSCs) from miR-21(-/-) mice show enhanced immunosuppressive function by more TGF-beta1 secretion and induce more CD4(+) Foxp3(+) regulatory T cells compared with wild-type BMMSCs in vitro, which anti-TGF-beta1 antibody abrogates. Mechanistically, miR-21 inhibits TGF-beta1 expression by targeting phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in BMMSCs. Downstream of PTEN, miR-21 promotes activation of Akt, and consequently increases activation of NF-kappaB pathway. Importantly, adoptive transfer of miR-21(-/-) BMMSCs into mice with experimental colitis more effectively ameliorates colonic inflammation in a TGF-beta1-dependent manner. Thus, these findings indicate a previously uncovered mechanism of miR-21 control immunoregulatory function of BMMSCs through TGF-beta1 inhibition. |
