Open AccessSimvastatin improves the homing of BMSC s via the PI 3K/ AKT /miR‐9 pathway
Author(s) -
Bing Weidong,
Pang Xinyan,
QU Qingxi,
Bai Xiao,
Yang Wenwen,
Bi Yanwen,
Bi Xiaolu
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12795
Subject(s) - simvastatin , protein kinase b , homing (biology) , phosphorylation , chemokine , chemistry , microbiology and biotechnology , cancer research , pi3k/akt/mtor pathway , signal transduction , biology , pharmacology , receptor , biochemistry , ecology
Bone marrow‐derived mesenchymal stem cells ( BMSC s) have great therapeutic potential for many diseases. However, the homing of BMSC s to injury sites remains a difficult problem. Recent evidence indicates that simvastatin stimulates AKT phosphorylation, and p‐ AKT affects the expression of chemokine ( CXC motif) receptor‐4 ( CXCR 4). Therefore, simvastatin may improve the expression of CXCR 4 in BMSC s, and micro RNA s (miRs) may participate in this process. In this study, we demonstrated that simvastatin increased both the total and the surface expression of CXCR 4 in BMSC s. Stromal cell‐derived factor‐1α ( SDF ‑1α)‐induced migration of BMSC s was also enhanced by simvastatin, and this action was inhibited by AMD 3100(a chemokine receptor antagonist for CXCR 4). The PI 3K/ AKT pathway was activated by simvastatin in this process, and LY 294002 reversed the overexpression of CXCR 4 caused by simvastatin. MiR‐9 directly targeted CXCR 4 in rat BMSC s, and simvastatin decreased miR‐9 expression. P‐ AKT affected the expression of miR‐9; as the phosphorylation of AKT increased, miR‐9 expression decreased. In addition, LY 294002 increased miR‐9 expression. Taken together, our results indicated that simvastatin improved the migration of BMSC s via the PI 3K/ AKT pathway. MiR‐9 also participated in this process, and the phosphorylation of AKT affected miR‐9 expression, suggesting that simvastatin might have beneficial effects in stem cell therapy.