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首页> 外文期刊>Journal of Cellular Physiology >Statin regulated ERK5 stimulates tight junction formation and reduces permeability in human cardiac endothelial cells
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Statin regulated ERK5 stimulates tight junction formation and reduces permeability in human cardiac endothelial cells

机译:他汀类药物监管ERK5刺激紧密连接形成和减少渗透在人类心脏内皮细胞

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摘要

The MEKK3/MEK5/ERK5 signaling axis is required for cardiovascular development in vivo. We analyzed the physiological role of ERK5 in cardiac endothelial cells and the consequence of activation of this kinase by the statin class of HMG Co‐A reductase inhibitor drugs. We utilized human cardiac microvascular endothelial cells (HCMECs) and altered ERK5 expression using siRNA mediated gene silencing or overexpression of constitutively active MEK5 and ERK5 to reveal a role for ERK5 in regulating endothelial tight junction formation and cell permeability. Statin treatment of HCMECs stimulated activation of ERK5 and translocation to the plasma membrane resulting in co‐localization with the tight junction protein ZO‐1 and a concomitant reduction in endothelial cell permeability. Statin mediated activation of ERK5 was a consequence of reduced isoprenoid synthesis following HMG Co‐A reductase inhibition. Statin pretreatment could overcome the effect of doxorubicin in reducing endothelial tight junction formation and prevent increased permeability. Our data provide the first evidence for the role of ERK5 in regulating endothelial tight junction formation and endothelial cell permeability. Statin mediated ERK5 activation and the resulting decrease in cardiac endothelial cell permeability may contribute to the cardioprotective effects of statins in reducing doxorubicin‐induced cardiotoxicity.
机译:MEKK3 / MEK5 / ERK5信号需要轴心血管体内发展。ERK5在心脏的生理作用内皮细胞和的结果他汀类激酶的活化HMG Co还原酶抑制剂药物。人类的心脏微血管内皮细胞使用核(HCMECs)和改变ERK5表达式介导的基因沉默或超表达持续活跃MEK5和ERK5展示作用在调节内皮ERK5紧结形成和细胞通透性。治疗ERK5 HCMECs刺激激活的质膜和易位导致公司定位与紧张结蛋白佐薇1和应承担的相应减少在内皮细胞的通透性。激活ERK5是减少的结果类异戊二烯合成后物流公司应承担的还原酶抑制。阿霉素的影响减少内皮紧密连接形成,防止增加渗透率。ERK5调节内皮细胞的作用形成和内皮细胞紧密连接渗透率。结果减少心脏内皮细胞的渗透可能导致他汀类药物在降低心血管效应阿霉素诱导毒性。

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