Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, China.
Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, China.
J Cell Physiol. 2021 Jul;236(7):5176-5192. doi: 10.1002/jcp.30223. Epub 2020 Dec 23.
TMEM173 has been reported to participate in endoplasmic reticulum stress, inflammation and immunology, all of which closely involved with cardiac hypertrophy. But its role in autophagy is not fully figured out. In our research, Tmem173 global knockout (KO) mice manifested more deteriorated hypertrophy, fibrosis, inflammatory infiltration and cardiac malfunction compared with wild type C57BL/6 mice after 6 weeks of transverse aortic constriction. And KO mice showed inhibited autophagosome degradation in myocardium observed under transmission electron microscope and in protein level. In in vitro experiments conducted in neonatal rat cardiomyocytes under phenylephrine treatment, the abundance of Tmem173 gene was negatively related to the abundance of LC3-Ⅱ and the number of red and yellow fluorescent dots, of which reflected the capacity of autophagosome degradation. These results indicated that TMEM173 might be a promoter of autophagic flux and protected against pressure overload-induced cardiac hypertrophy. It may serve as a potential therapeutic target for cardiac hypertrophy in the future.
TMEM173 已被报道参与内质网应激、炎症和免疫学，这些都与心肌肥厚密切相关。但其在自噬中的作用尚未完全阐明。在我们的研究中，与野生型 C57BL/6 小鼠相比，Tmem173 全局敲除（KO）小鼠在横主动脉缩窄 6 周后表现出更严重的心肌肥厚、纤维化、炎症浸润和心功能障碍。并且在透射电镜下和蛋白水平观察到 KO 小鼠心肌中的自噬体降解受到抑制。在苯肾上腺素处理的新生大鼠心肌细胞的体外实验中，Tmem173 基因的丰度与 LC3-Ⅱ的丰度和红色和黄色荧光斑点的数量呈负相关，这反映了自噬体降解的能力。这些结果表明，TMEM173 可能是自噬流的促进剂，可防止压力超负荷引起的心肌肥厚。它可能成为未来心肌肥厚的潜在治疗靶点。
