title: Effects of Exendin-4 on bone marrow mesenchymal stem cell proliferation, migration and apoptosis in vitro.
abstract: Mesenchymal stem cells (MSC) are regarded as an attractive source of therapeutic stem cells for myocardial infarction. However, their limited self-renewal capacity, low migration capacity and poor viability after transplantation hamper the clinical use of MSC; thus, a strategy to enhance the biological functions of MSC is required. Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, exerts cell-protective effects on many types of cells. However, little information is available regarding the influence of Ex-4 on MSC. In our study, MSC were isolated from bone marrow and cultured in vitro. After treatment with Ex-4, MSC displayed a higher proliferative capacity, increased C-X-C motif receptor 4 (CXCR4) expression and an enhanced migration response. Moreover, in H2O2-induced apoptosis, Ex-4 preserved mitochondrial function through scavenging ROS and balancing the expression of anti- and pro-apoptotic proteins, leading to the inhibition of the mitochondria-dependent cell death pathways and increased cell survival. Moreover, higher phospho-Akt (p-Akt) expression was observed after Ex-4 intervention. However, blockade of the PI3K/Akt pathway with inhibitors suppressed the above cytoprotective effects of Ex-4, suggesting that the PI3K/Akt pathway is partly responsible for Ex-4-mediated MSC growth, mobilization and survival. These findings provide an attractive method of maximizing the effectiveness of MSC-based therapies in clinical applications.
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Radiotherapy, Beijing Cancer Hospital, Beijing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shi
authors.affiliation: Department of Cardiology, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xin
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Shunyin
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Tian
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yundai
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D000077270:Exenatide; D006861:Hydrogen Peroxide / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014688:Venoms / Q000494:pharmacology*
chemical_list: D051017:Apoptosis Regulatory Proteins; C486264:Cxcr4 protein, rat; D010455:Peptides; D017382:Reactive Oxygen Species; D019718:Receptors, CXCR4; D014688:Venoms; D000077270:Exenatide; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt