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

ISSN 1007-7626

CN 11-3870/Q

中国生物化学与分子生物学报http ://cjbmb.bjmu.edu.cn

Chinese Journal of Biochemistry and Molecular Biology

2015年10月

31(10):1077 1084

DOI :10.13865/j.cnki.cjbmb.2015.10.11

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

李志超,杨海杰*,剧飞,冯培,马双平,连俊江,冯志伟

*

(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)

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 /EBP β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.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 信号通路中图分类号

Q254;Q257

TGF-β1Inhibits PI3K /Akt Signaling-mediated Adipogenic Differentiation of BMSCs through Activating Smad Pathway

LI Zhi-Chao ,YANG Hai-Jie *,JU Fei ,FENG Pei ,MA Shuang-Ping ,LIAN Jun-Jiang ,FENG Zhi-Wei *

(College of Life Science and Technology ,Xinxiang Medical University ,Xinxiang 453003,Henan ,China )

Abstract 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-β1

expression was significantly down-regulated in BMSCs during in vitro adpogenic differentiation.

Recombinant TGF-β1was demonstrated to inhibit the induction of adipocyte markers ,C /EBP-βand α-P2.TGF-β1activated the Smad pathway while blunted the insulin activation of PI3K /Akt signaling.In

the presence of Smad inhibitor ,the down-regulation of TGF-β1on C /EBP-βand α-P2expression was diminished ,and the TGF-β1-blunted PI3K /Akt signaling was restored.The results suggested that TGF-β1is involved in the regulation of BMSC adipogenic differentiation ,which and its effect is mediated

by the inhibition of PI3K /Akt activation on the Smad pathway.Key words transforming growth factor-β1(TGF-β1);mesenchymal stem cells ;adipogenic differentiation ;Smad pathway ;PI3K /Akt signaling 收稿日期:2015-03-12;接受日期:2015-06-08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*

联系人Tel :0373-*******;Fax :0373-*******;E-mail :hjyang _wmd@hotmail.com ;xxyxy-fzw@163.com Received :March 12,2015;Accepted :June 8;2015

Supported by National Natural Science Foundation of China (No.81450059),Intramural Science Fostering Foundation of Xinxiang Medical University (No.2013ZD115);Graduate Student Research and Innovation Project (No.YJSCX20407Z )

*Corresponding author Tel :+86-373-3831165;

E-mail :hjyang_wmd@hotmail.com ;xxyxy-fzw@163.com

骨髓间充质干细胞(bone marrow-derived mesenchymal stem cells ,BMSCs )是最早被发现并被

常用的间充质干细胞.BMSCs 具有自我更新和多向分化的能力.研究证实,

BMSCs 在体外可分化为成骨细胞、软骨细胞、脂肪细胞、神经细胞及肌肉细胞等多种组织细胞

[1]

.其中,BMSCs 在体外分化为脂

肪细胞是一个高度精细的调控过程,多种转录因子和信号通路在脂肪细胞的形成过程中发挥重要的作

用.在众多调控脂肪分化的转录因子中,过氧化物

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