He Jing, Yi Bin, Chen Yang, Huang Qing, Wang Huan, Lu Kaizhi, Fu Weiling
Department of Anesthesia, Southwest Hospital, The Third Military Medical University, Chongqing, China.
Department of Laboratory Medicine, Southwest Hospital, Third Military Medical University, Chongqing, China.
PLoS One. 2017 Apr 17;12(4):e0175443. doi: 10.1371/journal.pone.0175443. eCollection 2017.
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.
肝肺综合征（HPS）是晚期肝病的一种严重并发症，可显著增加死亡率。循环介质诱导的肺血管重塑（PVR）在HPS的发病机制中起重要作用，但其潜在机制尚不清楚。在本研究中，我们报道了HPS大鼠中内皮素-1（ET-1）上调而膜联蛋白A1（ANXA1）下调，并且ET-1在大鼠肺动脉平滑肌细胞（PASMCs）中以剂量依赖性方式降低ANXA1表达。然后，我们表明ANXA1可减少核p-ERK1/2积累并降低细胞周期蛋白D1表达，从而导致随后对PASMCs增殖的抑制。如先前报道，我们证实ET-1通过ANXA1的羰基化和降解降低ANXA1蛋白水平。总之，我们的研究将ET1-ANXA1-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。
