Myeloid differentiation protein 1 protected myocardial function against high-fat stimulation induced pathological remodelling
Myeloid differentiation protein 1 protected myocardial function against high-fat stimulation induced pathological remodelling
复制标题
骨髓分化蛋白1保护心肌功能免受高脂肪刺激引起的病理重塑
DOI：
10.1111/jcmm.14407
复制
发表时间：
2019-08-01
影响因子：
5.3
通讯作者：
Huang, He
中科院分区：
文献类型：
--
作者：
Shen, Cai-Jie;Kong, Bin;Huang, He
髓样分化因子1（MD - 1）是一种分泌蛋白，它通过与辐射防护蛋白105（RP105）相互作用来调节B细胞的免疫应答。免疫应答失调可能会促使心脏疾病的发生，然而MD - 1的作用仍不明确。我们的研究旨在探索MD - 1在肥胖诱导的心肌病中的功能和分子机制。用含有棕榈酸和油酸的游离脂肪酸（FFA）处理H9C2心肌细胞以模拟高脂刺激，并使用携带人MD - 1编码序列的腺病毒或针对MD - 1的短发夹RNA（shRNA）在体外实现MD - 1的过表达或敲低。构建MD - 1过表达或敲低的转基因小鼠，以在体内评估MD - 1对高脂饮食（HD）诱导的心肌病的影响。我们的结果显示，在受到FFA刺激48小时的H9C2细胞以及高脂饮食诱导20周的肥胖小鼠中，MD - 1均下调。在体内和体外，MD - 1的沉默通过增加心肌肥大和纤维化加速了高脂刺激诱导的心肌功能损伤，而MD - 1的过表达通过抑制心脏重构过程减轻了高脂饮食的影响。此外，在高脂处理后，MD - 1缺陷小鼠和H9C2细胞中的丝裂原活化蛋白激酶（MAPK）和核因子 - κB（NF - κB）通路过度激活。抑制MAPK和NF - κB通路对MD - 1沉默在高脂刺激诱导的病理重构中的不良影响具有心脏保护作用。总之，MD - 1通过对MAPK / NF - κB信号通路的负向调节来保护心肌功能免受高脂刺激诱导的心脏病理重构，为肥胖心肌病提供了可行的治疗策略。
Myeloid differentiation 1 (MD-1) is a secreted protein that regulates the immune response of B cell through interacting with radioprotective 105 (RP105). Disrupted immune response may contribute to the development of cardiac diseases, while the roles of MD-1 remain elusive. Our studies aimed to explore the functions and molecular mechanisms of MD-1 in obesity-induced cardiomyopathy. H9C2 myocardial cells were treated with free fatty acid (FFA) containing palmitic acid and oleic acid to challenge high-fat stimulation and adenoviruses harbouring human MD-1 coding sequences or shRNA for MD-1 overexpression or knockdown in vitro. MD-1 overexpression or knockdown transgenic mice were generated to assess the effects of MD-1 on high-fat diet (HD) induced cardiomyopathy in vivo. Our results showed that MD-1 was down-regulated in H9C2 cells exposed to FFA stimulation for 48 hours and in obesity mice induced by HD for 20 weeks. Both in vivo and in vitro, silencing of MD-1 accelerated myocardial function injury induced by HD stimulation through increased cardiac hypertrophy and fibrosis, while overexpression of MD-1 alleviated the effects of HD by inhibiting the process of cardiac remodelling. Moreover, the MAPK and NF-kappa B pathways were overactivated in MD-1 deficient mice and H9C2 cells after high-fat treatment. Inhibition of MAPK and NF-kappa B pathways played a cardioprotective role against the adverse effects of MD-1 silencing on high-fat stimulation induced pathological remodelling. In conclusion, MD-1 protected myocardial function against high-fat stimulation induced cardiac pathological remodelling through negative regulation for MAPK/NF-kappa B signalling pathways, providing feasible strategies for obesity cardiomyopathy.