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Role of JAK-STAT3 signaling pathway during neuronal differentiation of rat bone marrow mesenchymal stem cells

查看全文 作　　者：Huaiyong [1]Hao;Yongguang [2]Wang;Feng [1]Cheng;Baosheng [3]Huang;Heping [1]Tian;Xueliang [1]Dai;Lixin [1]Li 高影响力作者 机构地区：[1]Department of Neurosurgery, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China;[2]Department of Radiology, Zaozhuang Shizhong District People's HospitaI, Zaozhuang 277100, Shandong Province, China;[3]Department of Neurosurgery, BenQ Hospital Affiliated to Nanjing Medical University, Nanjing 210029, Jiangsu Province, China高影响力机构 出　　处：《Neural Regeneration Research》索引2010年第5卷第5期,共5页高影响力期刊 基　　金：the National Nature Science Foundation of China, No. 30973092;'Xingwei' Project Medical Emphasis Grant from Jiangsu Province, No. RC2007062 摘　　要：BACKGROUND: Recent studies regarding neuronal differentiation of mesenchymal stem cells (MSCs) have primarily focused on induction methods and transplantation in vivo.However,knowledge about the intrinsic regulatory mechanisms underlying neuronal induction of MSCs remains limited and unclear.OBJECTIVE: To elucidate the role of JAK-STAT3 signaling pathway during neuronal differentiationof MSCs using a combination of the JAK-STAT3 signaling inhibitor AG490 and growth factors.DESIGN,TIME AND SETTING: Neural,molecular,biomedical,in vitro experiment was performed at the Laboratory of Pharmacology,School of Pharmacy,Nanjing Medical University between Marchand December 2008 MATERIALS: An inhibitor of the JAK-STAT3 signaling pathway was purchased from Calbiochem,USA.Antibody kit for total and phosphorylated STAT3 was purchased from Cell Signaling,USA.METHODS: MSCs from passage 3 were assigned to non-induced,growth factor,and AG490 groups.MAIN OUTCOME MEASURE: The number of cells expressing neuron-specific enolase,microtubule-associated protein,and glial fibrillary acidic protein were determined by immunocytochemistry.Total and phosphorylated (Tyr705) expression levels of STAT3 protein were measured by Western blot analysis.RESULTS: MSCs were transdifferentiated into neuronaland astrocyte-like phenotypes throughthe induction of epidermal growth factor,basic fibroblast growth factor,and brain-derived neurotrophic factor.In addition,the JAK-STAT3 signaling pathway was significantly activated during neural differentiation.Expression of phosphorylated (Tyr705) STAT3 was inhibited with AG490 (5 μmol/L) prior to neural induction with epidermal growth factor,basic fibroblast growth factor,and brain-derived neurotrophic factor;proportion of astrocyte-like cells was significantly reduced (P < 0.01),and the proportion of neuronal-like phenotypes was significantly increased (P < 0.01).CONCLUSION: JAK-STAT3 signaling pathway was shown to regulate neuronal induction of bone marrow MSCs.The proportion of MSC-induced neuronal-like cells was increased following treatment with the JAK-STAT3 signaling inhibitor AG490. 关 键 词：JAK-STAT3 signaling pathway, mesenchymal stem cells AG490, neuronal induction NEURONS ASTROCYTES stem cells neural regeneration
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