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Knockdown of insulin-like growth factor 2 gene disrupts mitochondrial functions in the liver
Journal of Molecular Cell Biology ( IF 5.5 ) Pub Date : 2021-05-13 , DOI: 10.1093/jmcb/mjab030
Weiwei Gui 1 , Yiyi Zhu 2 , Shuiya Sun 1 , WeiFen Zhu 1 , Bowen Tan 3 , Hanxin Zhao 1 , Chengxin Shang 1 , Fenping Zheng 1 , Xihua Lin 1, 4 , Hong Li 1
Affiliation  

Even though insulin-like growth factor 2 (IGF2) has been reported to be overexpressed in nonalcoholic fatty liver disease (NAFLD), its role in the progression of NAFLD and the potential mechanism remain largely unclear. Using in vitro models, we found that IGF2 was the key overexpressed gene in steatosis, suggesting a possible association between IGF2 and NAFLD. Interestingly, loss-of-function experiments revealed that inhibition of IGF2 protein impaired mitochondrial biogenesis and respiration. It additionally disrupted the expression changes of mitochondrial fusion and fission-related proteins necessary in maintaining mitochondrial homeostasis. Consistently, IGF2 knockdown reduced the mitochondrial membrane potential and increased the production of reactive oxygen species. Mechanistically, IGF2 regulates mitochondrial functions by modulating the expression of SIRT1 and its downstream gene PGC1α. This research opens a new Frontier on the role of IGF2 in energy metabolism, which potentially participates in the development of NAFLD. As such, IGF2 is a potential therapeutic target against NAFLD.

中文翻译:

敲除胰岛素样生长因子 2 基因会破坏肝脏中的线粒体功能

尽管据报道胰岛素样生长因子 2 (IGF2) 在非酒精性脂肪性肝病 (NAFLD) 中过度表达,但其在 NAFLD 进展中的作用和潜在机制仍不清楚。使用体外模型,我们发现 IGF2 是脂肪变性的关键过表达基因,表明 IGF2 和 NAFLD 之间可能存在关联。有趣的是,功能丧失实验表明,抑制 IGF2 蛋白会损害线粒体的生物发生和呼吸。它还破坏了维持线粒体稳态所必需的线粒体融合和裂变相关蛋白的表达变化。一致地,IGF2 敲低降低了线粒体膜电位并增加了活性氧的产生。机械地,IGF2 通过调节 SIRT1 及其下游基因 PGC1α 的表达来调节线粒体功能。该研究开辟了 IGF2 在能量代谢中作用的新前沿,可能参与 NAFLD 的发展。因此,IGF2 是针对 NAFLD 的潜在治疗靶点。
更新日期:2021-05-13
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