MG53 suppresses NF-κB activation to mitigate age-related heart failure.
MG53 suppresses NF-κB activation to mitigate age-related heart failure.
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DOI：
10.1172/jci.insight.148375
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发表时间：
2021-09-08
期刊：
影响因子：
8
通讯作者：
Ma J
中科院分区：
文献类型：
--
作者：
Wang X;Li X;Ong H;Tan T;Park KH;Bian Z;Zou X;Haggard E;Janssen PM;Merritt RE;Pawlik TM;Whitson BA;Mokadam NA;Cao L;Zhu H;Cai C;Ma J
衰老与影响组织修复和再生能力的慢性氧化应激和炎症有关。MG53是一种TRIM家族蛋白，以氧化还原依赖的方式促进细胞膜损伤的修复。在这里，我们证明了MG53在衰竭的人类心脏和衰老的小鼠心脏中表达降低，同时NF-κB激活升高。我们评估了在老年小鼠中纵向、系统给药重组人MG53 （rhMG53）蛋白的安全性和有效性。超声心动图和压力-容量环路测量显示rhMG53治疗对改善老年小鼠心功能有有益作用。生化和组织学研究表明，rhMG53的心脏保护作用与抑制NF-κ b介导的炎症、减少衰老心脏中凋亡细胞死亡和氧化应激有关。在老年小鼠中反复给药rhMG53对主要重要器官功能没有不良影响。这些发现支持了rhMG53在治疗年龄相关性心功能下降方面的治疗价值。
Aging is associated with chronic oxidative stress and inflammation that affect tissue repair and regeneration capacity. MG53 is a TRIM family protein that facilitates repair of cell membrane injury in a redox-dependent manner. Here, we demonstrate that the expression of MG53 was reduced in failing human hearts and aged mouse hearts, concomitant with elevated NF-κB activation. We evaluated the safety and efficacy of longitudinal, systemic administration of recombinant human MG53 (rhMG53) protein in aged mice. Echocardiography and pressure-volume loop measurements revealed beneficial effects of rhMG53 treatment in improving heart function of aged mice. Biochemical and histological studies demonstrated that the cardioprotective effects of rhMG53 are linked to suppression of NF-κB–mediated inflammation, reducing apoptotic cell death and oxidative stress in the aged heart. Repetitive administration of rhMG53 in aged mice did not have adverse effects on major vital organ functions. These findings support the therapeutic value of rhMG53 in treating age-related decline in cardiac function.