机械敏感通道
细胞生物学
基因表达
横截面
罗亚
心肌细胞
体内
生物
生物物理学
化学
解剖
基因
信号转导
离子通道
遗传学
受体
作者
Shulin Cao,Kyle S. Buchholz,Philip Tan,Jennifer Stowe,Ariel Wang,Annabelle Fowler,Katherine R. Knaus,Ali Khalilimeybodi,Alexander C. Zambon,Jeffrey H. Omens,Jeffrey J. Saucerman,Andrew D. McCulloch
出处
期刊:American Journal of Physiology-heart and Circulatory Physiology
[American Physiological Society]
日期:2023-12-08
标识
DOI:10.1152/ajpheart.00562.2023
摘要
To identify how cardiomyocyte mechanosensitive signaling pathways are regulated by anisotropic stretch, micropatterned mouse neonatal cardiomyocytes were stretched primarily longitudinal or transverse to the myofiber axis. Four hours of static, longitudinal stretch induced differential expression of 557 genes, compared with 30 induced by transverse stretch, measured using RNA-seq. A logic-based ordinary differential equation model of the cardiac myocyte mechanosignaling network, extended to include the transcriptional regulation and expression of 784 genes, correctly predicted measured expression changes due to anisotropic stretch with 69% accuracy. The model also predicted published transcriptional responses to mechanical load in vitro or in vivo with 63-91% accuracy. The observed differences between transverse and longitudinal stretch responses were not explained by differential activation of specific pathways but rather by an approximately two-fold greater sensitivity to longitudinal than transverse stretch. In-vitro experiments confirmed model predictions that stretch-induced gene expression is more sensitive to angiotensin II and endothelin-1, via RhoA and MAP kinases, than to the three membrane ion channels upstream of calcium signaling in the network. Quantitative cardiomyocyte gene expression differs substantially with the axis of maximum principal stretch relative to the myofilament axis, but this difference is due primarily to differences in stretch sensitivity rather than to selective activation of mechanosignaling pathways.
科研通智能强力驱动
Strongly Powered by AbleSci AI