title: Simvastatin improves the homing of BMSCs via the PI3K/AKT/miR-9 pathway.
abstract: Bone marrow-derived mesenchymal stem cells (BMSCs) have great therapeutic potential for many diseases. However, the homing of BMSCs 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 (CXCR4). Therefore, simvastatin may improve the expression of CXCR4 in BMSCs, and microRNAs (miRs) may participate in this process. In this study, we demonstrated that simvastatin increased both the total and the surface expression of CXCR4 in BMSCs. Stromal cell-derived factor-1α (SDF-1α)-induced migration of BMSCs was also enhanced by simvastatin, and this action was inhibited by AMD 3100(a chemokine receptor antagonist for CXCR4). The PI3K/AKT pathway was activated by simvastatin in this process, and LY294002 reversed the overexpression of CXCR4 caused by simvastatin. MiR-9 directly targeted CXCR4 in rat BMSCs, 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, LY294002 increased miR-9 expression. Taken together, our results indicated that simvastatin improved the migration of BMSCs via the PI3K/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.
authors: Department of Cardiovascular Surgery, Qi Lu Hospital of Shandong University, Jinan, Shandong Province, China.
authors: Weidong
authors: W
authors: Bing
authors: Department of Cardiovascular Surgery, Qi Lu Hospital of Shandong University, Jinan, Shandong Province, China.
authors: Xinyan
authors: X
authors: Pang
authors: Department of Cardiovascular Surgery, Qi Lu Hospital of Shandong University, Jinan, Shandong Province, China.
authors: Qingxi
authors: Q
authors: Qu
authors: Department of Cardiovascular Surgery, Qi Lu Hospital of Shandong University, Jinan, Shandong Province, China.
authors: Xiao
authors: X
authors: Bai
authors: Department of Cardiovascular Surgery, Qi Lu Hospital of Shandong University, Jinan, Shandong Province, China.
authors: Wenwen
authors: W
authors: Yang
authors: Department of Cardiovascular Surgery, Qi Lu Hospital of Shandong University, Jinan, Shandong Province, China.
authors: Yanwen
authors: Y
authors: Bi
authors: School of Life Science of Shandong University, Jinan, Shandong Province, China.
authors: Xiaolu
authors: X
authors: Bi
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001596:Benzylamines; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D000080027:Cyclams; D005269:Femur / Q000166:cytology; D005786:Gene Expression Regulation; D006571:Heterocyclic Compounds / Q000494:pharmacology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D000924:Anticholesteremic Agents; D001596:Benzylamines; D054377:Chemokine CXCL12; D002867:Chromones; D000080027:Cyclams; D006571:Heterocyclic Compounds; D035683:MicroRNAs; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D019718:Receptors, CXCR4; D019821:Simvastatin; C486264:Cxcr4 protein, rat; C582333:MIRN9 microRNA, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C088327:plerixafor
keywords: AKT; BMSCs; CXCR4; microRNA; simvastatin