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Basic Res Cardiol:不同结论!外源性GDF11诱导心脏和骨骼肌功能紊乱及质量损耗。

2017-06-27 fengxiangxin MedSci原创

TGF-β超家族成员生长分化因子11(GDF11),与肌肉生长抑制素高度同源,同时也是胚胎发育和器官形成中必不可少的。以往有关GDF11影响成人组织的报告往往互相矛盾,其中一些描述了GDF11的抗衰老作用和促进心脏和骨骼肌再生活动作用,另一些则报告了其对心机和骨骼肌没有影响甚至有相反的影响。此研究中,研究者试图确定体内过剩的GDF11对心脏和骨骼肌的影响。

TGF-β超家族成员生长分化因子11(GDF11),与肌肉生长抑制素高度同源,同时也是胚胎发育和器官形成中必不可少的。以往有关GDF11影响成人组织的报告往往互相矛盾,其中一些描述了GDF11的抗衰老作用和促进心脏和骨骼肌再生活动作用,另一些则报告了其对心机和骨骼肌没有影响甚至有相反的影响。此研究中,研究者试图确定体内过剩的GDF11对心脏和骨骼肌的影响。

将GDF11分泌细胞注射入小鼠体内,等同于初步确定体内肌肉生长抑制素作用的模型。14天后,GDF11暴露的小鼠出现全身消瘦和心肌、骨骼肌功能紊乱。心肌质量丢失先于骨骼肌丢失发生。GDF11暴露后的10天内,心脏组织学及超声心动图检查显示:心室壁变薄,心肌细胞变小以及心功能下降。与骨骼肌质量损耗、肌纤维变细和强度变弱相关的变化在GDF11暴露13天后开始显现。心肌细胞和骨骼肌纤维的变化与SMAD2活化有关(泛素-蛋白酶体通路和自噬)。

因此,GDF11的体内试验导致了心肌和骨骼肌的损耗以及功能障碍甚至死亡。通过Western blotting检测,实验组血清GDF11水平比对照组增加了1.5倍。尽管GDF11的体内效应可能成剂量、途径和时间依赖性,但其引起的生理变化类似于肌肉生长抑制素和其他激活素受体的配体。

这些数据支持GDF11,像其他密切相关的TGF-β家族成员一样,引起心脏和骨骼肌的功能紊乱以及质量损耗。

原始出处:

Zimmers, T.A., Y. Jiang, M. Wang, et al., Exogenous GDF11 induces cardiac and skeletal muscle dysfunction and wasting. Basic Res Cardiol, 2017 Jul;112(4):48. doi: 10.1007/s00395-017-0639-9. Epub 2017 Jun 24.

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    2017-11-08 zhangph
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    2017-06-27 fengxiangxin301

    不错的基础研究

    0

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    2017-06-27 zwjnj2

    好基础研究赞

    0

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