The ET-1-mediated carbonylation and degradation of ANXA1 induce inflammatory phenotype and proliferation of pulmonary artery smooth muscle cells in HPS.
The ET-1-mediated carbonylation and degradation of ANXA1 induce inflammatory phenotype and proliferation of pulmonary artery smooth muscle cells in HPS.
复制标题
ET-1介导的ANXA1羰基化和降解诱导HPS中肺动脉平滑肌细胞的炎症表型和增殖
DOI：
10.1371/journal.pone.0175443
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Fu W
中科院分区：
文献类型：
--
作者：
He J;Yi B;Chen Y;Huang Q;Wang H;Lu K;Fu W
肝病综合征（HPS）是晚期肝病的严重并发症，其显著增加死亡率。循环介质诱导的肺血管重构（PVR）在HPS的发病机制中起重要作用，但其机制尚不清楚。本研究发现HPS大鼠肺动脉平滑肌细胞（PASMCs）内皮素-1（ET-1）表达上调，膜联蛋白A1（ANXA 1）表达下调，ET-1呈剂量依赖性降低ANXA 1的表达。ANXA 1可降低细胞核p-ERK 1/2的积累和cyclin D1的表达，从而抑制PASMCs的增殖。如前所述，我们证实ET-1通过ANXA 1的羰基化和降解降低ANXA 1蛋白水平。总之，我们的研究将ET 1-ANXA 1-细胞增殖的信号级联与阻断IPS相关PVR的潜在治疗策略联系起来。
Hepatopulmonary syndrome (HPS) is a serious complication of advanced liver disease, which markedly increases mortality. Pulmonary vascular remodelling (PVR) induced by circulating mediators plays an important role in the pathogenesis of HPS, while the underlying mechanism remains undefined. In the present study, we reported that endothelin-1 (ET-1) is up-regulated and annexin A1(ANXA1) is down-regulated in HPS rat, and ET-1 decreases the ANXA1 expression in a dose-dependent manner in rat pulmonary arterial smooth muscle cells (PASMCs). Then, we showed that ANXA1 can decrease nuclear p-ERK1/2 accumulation and decrease the cyclin D1 expression, thus resulting in the subsequent inhibition of PASMCs proliferation. As previously reported, we confirmed that ET-1 decreases the ANXA1 protein levels by the carbonylation and degradation of ANXA1. In conclusion, our research links the signaling cascade of ET1-ANXA1-cell proliferation to a potential therapeutic strategy for blocking IPS-associated PVR.