谷氨酰胺分解
压电1
机械敏感通道
机械转化
细胞生物学
运行x2
主动脉瓣
化学
癌症研究
转录因子
医学
生物
离子通道
内科学
生物化学
糖酵解
新陈代谢
受体
基因
作者
Guoheng Zhong,Sheng Su,Juncong Li,Hengli Zhao,Dongtu Hu,Jun Chen,Shichao Li,Yingwen Lin,Li Wen,Xiaochang Lin,Gaopeng Xian,Dingli Xu,Qingchun Zeng
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2023-06-02
卷期号:9 (22)
被引量:4
标识
DOI:10.1126/sciadv.adg0478
摘要
Hemodynamic overload and dysregulation of cellular metabolism are involved in development of calcific aortic valve disease (CAVD). However, how mechanical stress relates to metabolic changes in CAVD remains unclear. Here, we show that Piezo1, a mechanosensitive ion channel, regulated glutaminase 1 (GLS1)-mediated glutaminolysis to promote osteogenic differentiation of valve interstitial cells (VICs). In vivo, two models of aortic valve stenosis were constructed by ascending aortic constriction (AAC) and direct wire injury (DWI). Inhibition of Piezo1 and GLS1 in these models respectively mitigated aortic valve lesion. In vitro, Piezo1 activation induced by Yoda1 and oscillatory stress triggered osteogenic responses in VICs, which were prevented by Piezo1 inhibition or knockdown. Mechanistically, Piezo1 activation promoted calcium-dependent Yes-associated protein (YAP) activation. YAP modulated GLS1-mediated glutaminolysis, which enhanced osteogenic differentiation through histone acetylation of runt-related transcription factor 2 (RUNX2) promoters. Together, our work provided a cross-talk between mechanotransduction and metabolism in the context of CAVD.
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