肌生成抑制素
纤维化
心脏纤维化
心力衰竭
心肌细胞
内科学
生物
骨骼肌
内分泌学
调节器
心功能曲线
心肌
Cre重组酶
肌肉肥大
细胞生物学
医学
转基因
遗传学
转基因小鼠
基因
作者
Nadine Biesemann,Luca Mendler,Sawa Kostin,Astrid Wietelmann,Thilo Borchardt,Thomas Braun
标识
DOI:10.1007/s00441-015-2139-2
摘要
Myostatin, a member of the TGF-β superfamily of secreted growth factors, is a negative regulator of skeletal muscle growth. In the heart, it is expressed at lower levels compared to skeletal muscle but up-regulated under disease conditions. Cre recombinase-mediated inactivation of myostatin in adult cardiomyocytes leads to heart failure and increased mortality but cardiac function of surviving mice is restored after several weeks probably due to compensatory expression in non-cardiomyocytes. To study long-term effects of increased myostatin expression in the heart and to analyze the putative crosstalk between cardiomyocytes and fibroblasts, we overexpressed myostatin in cardiomyocytes. Increased expression of myostatin in heart muscle cells caused interstitial fibrosis via activation of the TAK-1-MKK3/6-p38 signaling pathway, compromising cardiac function in older mice. Our results uncover a novel role of myostatin in the heart and highlight the necessity for tight regulation of myostatin to maintain normal heart function.
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