从拉伸到信号:YAP1和PIEZO2在膀胱尿路上皮细胞感知中的作用

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ABSTRACT:ObjectiveTo explore the roles of the mechanoreceptor Yes-associated protein l(YAPl)and piezo type mechanosensitive ion channel component 2(PIEZO2)in mechanotransduction in mouse bladder urothelial cels.Methods Mousebladderurothelialcellsweresubjected tomecanicalstretchingusing theFX-6oTcellstretching systemandtreated with the YAPl-specific inhibitor verteporfin (VP).The expressions of PIEZO2,YAPl and connective tissue growth factor (CTGF)atthemRNA and protein levels,as wellas changes incelular adenosine triphosphatase(ATP)concentration,were detected using reverse transcription quantitative PCR(RT-qPCR)and Western blotting(WB).ResultsAfter stretching stimulation,under the fluorescence microscope,itwas observedthatthediameterlengthofthestretchedcels werelongerthan that before stretching,and the difference was statistically significant ( .The expressions ofYAP1,PIEZO2 and CTGF atthe mRNAand protein levels were increased in the stretched group compared to those of the non-stretched group( P< 0.05).VP efectively reduced the expresions of YAP1,PIEZO2 and CTGF at the mRNA and protein levels after stretching stimulation ( P<0.05 . Stretching stimulation significantly increased the intracellular ATP concentration,while VP was able to inhibit the increase in ATP concentration,with a statistically significant difference ( P<0.000 1) .ConclusionStretching stimulationincreased theexpressions of YAPland PIEZO2 inbladderurothelialcellsand promoted thereleaseof ATP; verteporfininhibitedtheincreaseinYAPlactivityandtheoverexpresionof PIEZO2causedbystretching,therebyreducingthe releaseof ATP.It is suggsted that mousebladder urothelial celsmay primarilysense mechanical signals through theYAPlPIEZO2-ATP pathway.

KEY WORDS:bladderurothelialcels;mechanical signal transduction;piezo type mechanosensitive ion channelcomponent; Yes-associated protein l ;connective tissue growth factor

摘要:目的探讨机械感受器Yes相关蛋白1(YAP1)和压电型机械敏感离子通道蛋白2(PIEZO2)在小鼠膀胱尿路上皮细胞机械信号转导中的作用机制。(剩余10858字)

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