Department of Surgery, Division of Cardiac Surgery, Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA.
TRIM-edicine, Inc., Columbus, Ohio, USA.
JCI Insight. 2021 Sep 8;6(17):e148375. doi: 10.1172/jci.insight.148375.
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.
衰老是与慢性氧化应激和炎症相关的，这些会影响组织修复和再生能力。MG53 是一种 TRIM 家族蛋白，它以依赖氧化还原的方式促进细胞膜损伤的修复。在这里，我们证明在衰竭的人心和衰老的老鼠心脏中，MG53 的表达减少，同时 NF-κB 激活升高。我们评估了重组人 MG53（rhMG53）蛋白在老年小鼠中的长期、系统给药的安全性和有效性。超声心动图和压力-容积环测量显示 rhMG53 治疗可改善老年小鼠的心脏功能。生化和组织学研究表明，rhMG53 的心脏保护作用与抑制 NF-κB 介导的炎症有关，可减少衰老心脏中的凋亡细胞死亡和氧化应激。在老年小鼠中重复给予 rhMG53 不会对主要重要器官功能产生不良影响。这些发现支持 rhMG53 在治疗与年龄相关的心脏功能下降方面的治疗价值。
