TGF-β1通过激活Smad信号途径抑制PI3K/AKT信号介导的BMSC成脂分化  

TGF-β1 Inhibits PI3K/Akt Signaling-mediated Adipogenic Differentiation of BMSCs through Activating Smad Pathway

作　　者：李志超[1] 杨海杰[1] 剧飞 冯培[1] 马双平[1] 连俊江 冯志伟[1] 

机构地区：[1]新乡医学院生命科学技术学院,河南省干细胞与生物治疗技术研究中心,河南新乡453003

出　　处：《中国生物化学与分子生物学报》2015年第10期1077-1084,共8页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家科学自然基金(81450059)资助项目;新乡医学院校内培育基金(No.2013ZD115);研究生创新课题(YJSCX20407Z)资助项目~~

摘　　要：转化生长因子β1(TGF-β1)是参与骨髓间充质干细胞(BMSCs)脂肪定向分化的重要调节因子,其具体的调节机制尚不清楚.本研究证明,BMSCs在体外分化为脂肪细胞的过程中,TGF-β1的基因表达显著下调,重组TGF-β1能够抑制BMSCs体外脂肪细胞定向分化,其分化的标志蛋白C/EBPβ和αP2的表达水平显著降低.TGF-β1在激活Smad信号通路的同时,还抑制胰岛素(脂肪分化的主要诱导剂)对PI3K/Akt信号通路的激活.加入Smad特异性阻断剂后,C/EBP-β和α-P2的诱导表达恢复正常,同时PI3K/Akt信号通路的活化亦得以恢复.结果提示,TGF-β1可通过Smad信号通路干扰脂肪细胞分化的核心信号通路-PI3K/Akt的活化,从而实现对BMSCs脂肪分化的抑制.该研究结果为肥胖等导致的心血管疾病或Ⅱ型糖尿病等的临床治疗提供有价值的参考.Transformation growth factor-β1（ TGF-β1） is a regulator of adipogenic differentiation of bone marrow-derived mesenchymal stem cells（ BMSCs）. In the present study,we demonstrated that TGF-β1expression was significantly down-regulated in BMSCs during in vitro adpogenic differentiation.Recombinant TGF-β1 was demonstrated to inhibit the induction of adipocyte markers,C/EBP-β and α-P2. TGF-β1 activated the Smad pathway while blunted the insulin activation of PI3 K/Akt signaling. In the presence of Smad inhibitor,the down-regulation of TGF-β1 on C/EBP-β and α-P2 expression was diminished,and the TGF-β1-blunted PI3 K/Akt signaling was restored. The results suggested that TGF-β1 is involved in the regulation of BMSC adipogenic differentiation,which and its effect is mediated by the inhibition of PI3 K/Akt activation on the Smad pathway.

关 键 词：转化生长因子β1 间充质干细胞 脂肪细胞分化 SMAD信号通路 PI3K/Akt信号通路 

分 类 号：Q254[生物学—细胞生物学] Q257