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