首页> 外文期刊>Endothelium: Journal of endothelial cell research >Endothelial connexin 37, connexin 40, and connexin 43 respond uniquely to substrate and shear stress.
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Endothelial connexin 37, connexin 40, and connexin 43 respond uniquely to substrate and shear stress.

机译:内皮细胞连接蛋白37,连接蛋白40和连接蛋白43对底物和剪切应力具有独特的响应。

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摘要

Endothelial connexins have been linked to atherosclerosis and hypertension; however, little is know about their sensitivity to stimuli and individual functions. This study investigates the responses of endothelial connexin 37, connexin 40, and connexin 43 (Cx37, Cx40, and Cx43) to shear stress and substrate. Human endothelial cells were seeded on adsorbed collagen or a collagen gel containing smooth muscle cells and exposed to static or laminar shear stress. Connexin mRNA, protein, and gap junction communication were examined. Endothelial monolayers were treated with connexin-specific short interfering RNA (siRNA) and evaluated for communication, proliferation, and morphology under static and shear stress. Results show differential responses of Cx37, Cx40, and Cx43 to substrate and shear stress with reduced communication after shear exposure. RNA interference of individual connexins resulted in expression change of nontarget connexins, which suggests linked expression. Gap junction communication under static conditions is reduced following Cx43 siRNA treatment. Endothelial cells are more elongated with RNA interference (RNAi) targeting Cx40. In conclusion, endothelial connexins demonstrated novel sensitivity to mechanical environment and substrate. Individual isotypes show differential responses and RNAi knockdown provides new insight into connexin function and potential roles in the vasculature.
机译:内皮连接蛋白与动脉粥样硬化和高血压有关。然而,对其刺激和个体功能的敏感性知之甚少。本研究调查了内皮连接蛋白37,连接蛋白40和连接蛋白43(Cx37,Cx40和Cx43)对剪切应力和底物的反应。将人内皮细胞接种在吸附的胶原蛋白或含有平滑肌细胞的胶原蛋白凝胶上,并暴露于静态或层流剪切应力下。检查了连接蛋白的mRNA,蛋白质和间隙连接通讯。用连接蛋白特异性短干扰RNA(siRNA)处理内皮细胞单层,并评估其在静态和剪切应力下的通讯,增殖和形态。结果显示,Cx37,Cx40和Cx43对基材和剪切应力的响应不同,剪切暴露后的连通性降低。个别连接蛋白的RNA干扰导致非目标连接蛋白的表达发生变化,这暗示了连锁表达。 Cx43 siRNA处理后,静态条件下的间隙连接通讯减少。内皮细胞在靶向Cx40的RNA干扰(RNAi)的作用下更加伸长。总之,内皮连接蛋白表现出对机械环境和基质的新型敏感性。单个同种型显示出不同的反应,RNAi敲低为连接蛋白功能和在脉管系统中的潜在作用提供了新的见识。

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