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Myotubularin-related protein 14 suppresses cardiac hypertrophy by inhibiting Akt.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2020-02-20 , DOI: 10.1038/s41419-020-2330-6 Jie-Lei Zhang 1 , Dian-Hong Zhang 2 , Ya-Peng Li 2 , Lei-Ming Wu 2 , Cui Liang 2 , Rui Yao 2 , Zheng Wang 2 , Sheng-Dong Feng 3 , Zhong-Min Wang 4 , Yan-Zhou Zhang 2
Cell Death & Disease ( IF 8.1 ) Pub Date : 2020-02-20 , DOI: 10.1038/s41419-020-2330-6 Jie-Lei Zhang 1 , Dian-Hong Zhang 2 , Ya-Peng Li 2 , Lei-Ming Wu 2 , Cui Liang 2 , Rui Yao 2 , Zheng Wang 2 , Sheng-Dong Feng 3 , Zhong-Min Wang 4 , Yan-Zhou Zhang 2
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Cardiac hypertrophy (CH) is an independent risk factor for many cardiovascular diseases, and is one of the primary causes of morbidity and mortality in elderly people. Pathological CH involves excessive protein synthesis, increased cardiomyocyte size, and ultimately the development of heart failure. Myotubularin-related protein 14 (MTMR14) is a member of the myotubularin (MTM)-related protein family, which is involved in apoptosis, aging, inflammation, and autophagy. However, its exact function in CH is still unclear. Herein, we investigated the roles of MTMR14 in CH. We show that MTMR14 expression was increased in hypertrophic mouse hearts. Mice deficient in heart MTMR14 exhibited an aggravated aortic-banding (AB)-induced CH phenotype. In contrast, MTMR14 overexpression prevented pressure overload-induced hypertrophy. At the molecular level, prevention of CH in the absence of MTMR14 involved elevations in Akt pathway components, which are key elements that regulate apoptosis and cell proliferation. These results demonstrate that MTMR14 is a new molecular target for the treatment of CH.
中文翻译：
肌管蛋白相关蛋白14通过抑制Akt抑制心脏肥大。
心脏肥大（CH）是许多心血管疾病的独立危险因素，并且是老年人发病和死亡的主要原因之一。病理性CH涉及过多的蛋白质合成，增加的心肌细胞大小，并最终导致心力衰竭。肌管蛋白相关蛋白14（MTMR14）是肌管蛋白（MTM）相关蛋白家族的成员，与细胞凋亡，衰老，炎症和自噬有关。但是，其在CH中的确切功能仍不清楚。本文中，我们研究了MTMR14在CH中的作用。我们显示出肥大小鼠心脏中MTMR14表达增加。心脏MTMR14缺乏的小鼠表现出加重的主动脉束带（AB）诱导的CH表型。相反，MTMR14的过量表达可防止压力超负荷引起的肥大。在分子水平上 在没有MTMR14的情况下预防CH涉及到Akt途径组分的升高，这是调节细胞凋亡和细胞增殖的关键因素。这些结果表明，MTMR14是治疗CH的新分子靶标。
更新日期：2020-02-20
中文翻译：
肌管蛋白相关蛋白14通过抑制Akt抑制心脏肥大。
心脏肥大（CH）是许多心血管疾病的独立危险因素，并且是老年人发病和死亡的主要原因之一。病理性CH涉及过多的蛋白质合成，增加的心肌细胞大小，并最终导致心力衰竭。肌管蛋白相关蛋白14（MTMR14）是肌管蛋白（MTM）相关蛋白家族的成员，与细胞凋亡，衰老，炎症和自噬有关。但是，其在CH中的确切功能仍不清楚。本文中，我们研究了MTMR14在CH中的作用。我们显示出肥大小鼠心脏中MTMR14表达增加。心脏MTMR14缺乏的小鼠表现出加重的主动脉束带（AB）诱导的CH表型。相反，MTMR14的过量表达可防止压力超负荷引起的肥大。在分子水平上 在没有MTMR14的情况下预防CH涉及到Akt途径组分的升高，这是调节细胞凋亡和细胞增殖的关键因素。这些结果表明，MTMR14是治疗CH的新分子靶标。
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