骨形态发生蛋白7对 C2C12及 HepG2细胞胰岛素信号传导的负调控作用研究  

Bone morphogenetic protein-7 negatively regulates insulin signal transduction in C2C12 myotubes and HepG2 hepatocytes

作　　者：姚丽丽[1] 成兴波[1] 王美红[2] 崔世维[3] 唐祝奇[3] 孙诚[2] 

机构地区：[1]苏州大学附属第一医院内分泌科 215006 [2]南通大学神经再生重点实验室 [3] 南通大学附属医院内分泌科

出　　处：《中华内分泌代谢杂志》2016年第2期128-132,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金（31271260）;江苏省高校自然科学基金重点项目（14KJA180006）.

摘　　要：目的：研究骨形态发生蛋白7（BMP7）对骨骼肌细胞C2C12及肝细胞HepG2胰岛素信号途径的影响，并初步探讨其作用机制。方法用不同浓度BMP7处理骨骼肌细胞C2C12及肝实质细胞HepG2，用Western印迹方法检测胰岛素信号途径中各主要蛋白的变化。同时，提取细胞总RNA后用定量PCR方法检测BMP7对胰岛素效应分子基因表达的影响。另外，用Western印迹方法检测BMP7对JNK信号途径的影响。结果在分化的C2 C12与HepG2细胞中，胰岛素处理可显著增加磷酸化胰岛素受体（ p-IR）、磷酸化Akt（ p-Akt）及磷酸化糖原合成酶3β（ p-GSK3β）的表达，并促进葡萄糖向细胞内的转运（ P＜0．05）。而BMP7处理可明显降低胰岛素对这些磷酸化蛋白的刺激，并可抑制胰岛素诱导的葡萄糖向细胞内的转运（P＜0．05）。 BMP7处理对胰岛素效应分子Akt1、胰岛素样生长因子受体（Igf1r）、胰岛素受体（Insr）及胰岛素受体底物（Irs1）的基因表达均没有显著影响。在HepG2细胞中，BMP7处理5 min即可提高磷酸化JNK信号通路，随着作用时间的延长这种促进作用逐渐减弱。结论 BMP7降低HepG2及C2C12细胞中的胰岛素信号传递，这种抑制作用可能是通过激活JNK信号途径实现的。Objective To investigate the effects of bone morphogenetic protein-7 （ BMP7 ） on insulin signaling transduction in C2C12 myotubes and HepG2 hepatocytes, and the underlying mechanisms were studied preliminarily.Methods The C2C12 myotubes and HepG2 cells were treated with BMP7 at different concentrations.The insulin signal transduction was analyzed by Western blot.Meanwhile, total RNA was extracted and quantitative PCR was employed for detecting the effects of BMP7 on gene expressions of effectors involved in insulin signal pathway.Furthermore, JNK signal pathway was also measured.Results The protein levels of p-IR, p-Akt and p-GSK3β, as well as glucose uptake, were significantly stimulated by insulin in the C2C12 myotubes and HepG2 cells.However, these stimulations induced by insulin were largely attenuated by BMP7.The mRNA levels of Akt1, Igf1r, Insr, and Irs1 were not altered by the treatment of BMP7.The JNK signal pathway was activated by a 5-min exposure of BMP7 in the HepG2 cells, and this activation was gradually reduced along with the treating time.Conclusion BMP7 attenuates the insulin signal transduction in the HepG2 cells and C2C12 myotubes, and this attenuation effect may be through JNK activation.

关 键 词：骨形态发生蛋白-7 胰岛素信号传导 葡萄糖 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]