Lipopolysaccharide Induces Human Pulmonary Micro-Vascular Endothelial Apoptosis via the YAP Signaling Pathway.
Lipopolysaccharide Induces Human Pulmonary Micro-Vascular Endothelial Apoptosis via the YAP Signaling Pathway.
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脂多糖通过 YAP 信号通路诱导人肺微血管内皮细胞凋亡
DOI：
10.3389/fcimb.2016.00133
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发表时间：
2016
影响因子：
5.7
通讯作者：
Huan J
中科院分区：
文献类型：
--
作者：
Yi L;Huang X;Guo F;Zhou Z;Chang M;Tang J;Huan J
在败血症条件下，革兰氏阴性细菌脂多糖(LPS)可导致肺血管渗漏的病理性增加。脂多糖诱导的人肺微血管内皮细胞(HPMEC)凋亡启动并加重微血管高通透性和急性肺损伤(ALI)。已有研究表明，内源性细胞凋亡通路的激活在内毒素诱导的内皮细胞凋亡中起着至关重要的作用。YAP在肿瘤细胞凋亡中对固有的凋亡途径具有正向调节作用。然而，YAP蛋白在脂多糖诱导的HPMEC凋亡中的潜在作用尚未确定。在本研究中，我们发现内毒素诱导的YAP活化和核积聚加速了HPMECs的凋亡。脂多糖通过增加Y357的磷酸化诱导YAP从胞浆到细胞核的易位，导致YAP与转录因子p73的相互作用。此外，小干扰RNA(SiRNA)抑制YAP不仅能抑制脂多糖诱导的HPMEC的凋亡，而且还能调节p73介导的bax上调和bcl2下调。综上所述，我们的结果表明YAP/p73/(bax和bcl2)/caspase-3信号通路的激活在内毒素诱导的HPMEC凋亡中起着关键作用。抑制YAP可能是脓毒症肺损伤的一种潜在的治疗策略。
Gram-negative bacterial lipopolysaccharide (LPS) induces a pathologic increase in lung vascular leakage under septic conditions. LPS-induced human pulmonary micro-vascular endothelial cell (HPMEC) apoptosis launches and aggravates micro-vascular hyper-permeability and acute lung injury (ALI). Previous studies show that the activation of intrinsic apoptotic pathway is vital for LPS-induced EC apoptosis. Yes-associated protein (YAP) has been reported to positively regulate intrinsic apoptotic pathway in tumor cells apoptosis. However, the potential role of YAP protein in LPS-induced HPMEC apoptosis has not been determined. In this study, we found that LPS-induced activation and nuclear accumulation of YAP accelerated HPMECs apoptosis. LPS-induced YAP translocation from cytoplasm to nucleus by the increased phosphorylation on Y357 resulted in the interaction between YAP and transcription factor P73. Furthermore, inhibition of YAP by small interfering RNA (siRNA) not only suppressed the LPS-induced HPMEC apoptosis but also regulated P73-mediated up-regulation of BAX and down-regulation of BCL-2. Taken together, our results demonstrated that activation of the YAP/P73/(BAX and BCL-2)/caspase-3 signaling pathway played a critical role in LPS-induced HPMEC apoptosis. Inhibition of the YAP might be a potential therapeutic strategy for lung injury under sepsis.
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影响因子：
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作者：
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影响因子：
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