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| 血管紧张素II通过PI3K/Akt/FOXO1信号通路诱导骨骼肌细胞萎缩 |
| Angiotensin II induces skeletal muscle cell atrophy through the PI3K/Akt/FOXO1 signaling pathway |
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| DOI：10.3969/j.issn.1006-7108.2021.10.008 |
| 中文关键词: 血管紧张素II 成肌细胞 肌管 肌肉萎缩 PI3K/Akt/FOXO1信号通路 |
| 英文关键词:angiotensin II myoblast myotube muscle atrophy PI3K/Akt/FOXO1 signaling pathway |
| 基金项目:国家自然科学基金（82074468）；上海市优秀学术带头人计划（19XD1423800）；上海市科技创新行动计划（21400760400）；上海市市级医疗卫生优秀学科带头人培养计划（2018BR03）；上海中医药大学“研究生创新培养”专项科研项目（Y2020003） |
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| 中文摘要: |
| 目的 探讨血管紧张素II（Ang II）对骨骼肌细胞的调控作用及其作用机制。方法 使用Ang II及其1型受体（AT1R）拮抗剂（ARB）奥美沙坦干预C2C12成肌细胞，分为Control、Ang II和Ang II+ ARB三组。使用2 %马血清诱导成肌细胞分化为肌管细胞。免疫荧光染色检测肌管细胞的平均面积改变，Western blot检测肌管细胞泛素连接酶、生肌调节因子（MRFs）和PI3K/Akt/FOXO1信号通路蛋白表达的变化。结果 免疫荧光染色显示，Ang II干预后，肌管细胞的平均直径和面积减小（P < 0.001）；使用奥美沙坦干预后，肌管细胞平均直径和面积明显增大（P < 0.01）。Western blot显示，Ang II干预后，肌管细胞p-PI3K/PI3K（P < 0.01），p-Akt/Akt （P < 0.001）和p-FOXO1/FOXO1（P < 0.01）的比率降低；MURF1（P < 0.05）和MAFbx（P < 0.001）蛋白表达明显升高，MHC（P < 0.01）和MyoD（P < 0.05）蛋白表达明显降低；使用奥美沙坦处理后，能够减轻Ang II对肌管细胞的干预作用。结论 Ang II能够通过抑制PI3K/Akt/FOXO1信号通路的磷酸化，促进蛋白的降解，抑制蛋白的合成，诱导骨骼肌细胞萎缩。 |
| 英文摘要: |
| Objective To investigate the regulation and mechanism of angiotensin II (Ang II) on skeletal muscle cells. Methods C2C12 myoblasts were divided into three groups（Control, Ang II and Ang II+ ARB）according to their treatment with Ang II or Olmesartan. 2% horse serum was used to induce myoblasts differentiated into myotubes. Myotubes average area were detected by immunofluorescence staining, and Western blot was used to test the changes in protein expressions of muscle-specific ubiquitin ligases, myogenic regulatory factors (MRFs) and PI3K/Akt/FOXO1 signaling pathway. Results Immunofluorescence staining showed that the average diameter and area of myotubes decreased after Ang II treatment and these phenotypes of myotubes could be markedly reversed (P < 0.01) by Ang II type 1 receptor, olmesartan. Additionally, the protein level of the muscle-specific ubiquitin ligases including MURF1 (P < 0.05) and MAFbx (P < 0.001) were up-regulated induced by Ang II, while the ratio of p-PI3K/PI3K (P < 0.01), p-Akt/Akt (P < 0.001) and p-FOXO1/FOXO1 (P < 0.01) as well as MRFs including MHC (P < 0.01) and MyoD (P < 0.05) were down-regulated, and Olmesartan treatment could attenuate the effect of Ang II on myotube proteins. Conclusion Ang II can promote protein degradation and inhibit protein synthesis to induce muscle cell atrophy by inhibiting the phosphorylation of PI3K/Akt/FOXO1 signaling pathway. |
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