MiR-21 Modulates the Immunoregulatory Function of Bone Marrow Mesenchymal Stem Cells Through the PTEN/Akt/TGF-β1 Pathway. (1st July 2015)

• Record Type: Journal Article
• Authors: Wu, Tingting; Liu, Yi; Fan, Zhipeng; Xu, Junji; Jin, Luyuan; Gao, Zhenhua; Wu, Zhifang; Hu, Lei; Wang, Jinsong; Zhang, Chunmei; Chen, Wanjun; Wang, Songlin
• Is Part Of: Stem cells. Volume 33:Number 11(2015:Nov.)
• Page Start: 3281
• Page End: 3290
• Publication Date: 2015-07-01
• Subjects: miR-21 -- Immunoregulation -- Mesenchymal stem cells -- Transforming growth factor-β1 -- PTEN; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2081
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: 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-β1 (TGF-β1) in MSCs. Consistently, bone marrow MSCs (BMMSCs) from miR-21 −/− mice show enhanced immunosuppressive function by more TGF-β1 secretion and induce more CD4 + Foxp3 + regulatory T cells compared with wild-type BMMSCs in vitro, which anti-TGF-β1 antibody abrogates. Mechanistically, miR-21 inhibits TGF-β1 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-κB pathway. Importantly, adoptive transfer of miR-21 −/− BMMSCs into mice with experimental colitis more effectively ameliorates colonic inflammation in a TGF-β1-dependent manner. Thus, these findings indicate a previously uncovered mechanism of miR-21 control immunoregulatory function of BMMSCs through TGF-β1 inhibition. Stem Cells 2015;33:3281–3290