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Dioscin elevates lncRNA MANTIS in therapeutic angiogenesis for heart diseases
Aging Cell ( IF 8.0 ) Pub Date : 2021-06-03 , DOI: 10.1111/acel.13392
Chuiyu Kong 1 , Dayin Lyu 1 , Chang He 1 , Rui Li 1 , Qiulun Lu 1
Affiliation  

Dioscin has been widely used in clinics for coronary artery disease (CAD) treatment for years in China. However, the underlying mechanism for Dioscin-mediated cardioprotective effect has not been elucidated. Here, we showed that Dioscin significantly rescues the cardiac function in mouse model of myocardial infarction (MI), accompanied by the reduction of cardiac fibrosis and apoptosis, resulting from elevated angiogenesis. Mechanistically, Dioscin promotes the proliferation and migration of hypoxic endothelial cells via the up-regulation of lncRNA MANTIS, which serves as a scaffolding lncRNA within a chromatin remodeling complex. Meanwhile, it enables pol II binding to the transcription start sites, which leads to induced expression of angiogenesis-related genes, including SOX18, SMAD6, and COUP-TFII. Conversely, IncRNA MANTIS silencing prevents Dioscin-induced migration and angiogenesis in hypoxic endothelial cells. Taken together, these data provide new insights that clarifies the cardioprotective effects of Dioscin against myocardial infarcted injury and confirms the effect on angiogenic activity of endothelial cells. This will build a solid theoretical basis for clinical therapeutic strategies.
更新日期:2021-07-16
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