Gao Jing, Chen Lin, Zeng Jing, Cui Jian, Ning Jiao-lin, Wang Guan-song, Belguise Karine, Wang Xiaobo, Qian Gui-sheng, Lu Kai-zhi, Yi Bin
Department of Anesthesia, Southwest Hospital, the Third Military Medical University, Chongqing 400038, China.
Mol Biosyst. 2015 Nov;11(11):3040-7. doi: 10.1039/c5mb00347d.
Hepatopulmonary syndrome (HPS) is characterized by arterial oxygenation defects induced by intrapulmonary vascular dilation (IPVD). Pulmonary vascular remodeling (PVR) is an important pathological feature of IPVD; however, the details regarding the underlying mechanisms of this process remain undefined. Recent studies have determined that the abnormal migration of pulmonary arterial smooth muscle cells (PASMCs) plays a role in the pathogenesis of the PVR associated with HPS. Additionally, aquaporin 1 (AQP1) not only functions as a water channel molecule but also promotes cell migration by facilitating water transport in the lamellipodia of migrating cells. Common bile duct ligation (CBDL) rat is a well-accepted HPS model; we determined that the immunoperoxidase labeling of AQP1 was enhanced in the media of the pulmonary vessels in CBDL rats. HPS rat serum mediated the overexpression of AQP1 in PASMCs, and also upregulated PASMC migration. Small interfering RNAs (siRNAs) that targeted rat AQP1 caused significant downregulation of AQP1, which resulted in decreased PASMC migration. Furthermore, the inhibition of the p38-MAPK pathway abolished AQP1-dependent PASMC migration. In conclusion, this study demonstrated that AQP1 enhanced PASMC migration via the p38-MAPK pathway in rat with HPS and may represent a potential therapeutic strategy in the setting of pulmonary vascular remodeling associated with HPS.
肝肺综合征（HPS）的特征是由肺内血管扩张（IPVD）引起的动脉氧合缺陷。肺血管重塑（PVR）是IPVD的一个重要病理特征；然而，关于这一过程的潜在机制的细节仍不明确。最近的研究已经确定，肺动脉平滑肌细胞（PASMCs）的异常迁移在与HPS相关的PVR发病机制中起作用。此外，水通道蛋白1（AQP1）不仅作为一种水通道分子发挥作用，还通过促进迁移细胞板状伪足中的水运输来促进细胞迁移。胆总管结扎（CBDL）大鼠是一种公认的HPS模型；我们确定，在CBDL大鼠肺血管中膜，AQP1的免疫过氧化物酶标记增强。HPS大鼠血清介导PASMCs中AQP1的过表达，并且还上调PASMC迁移。靶向大鼠AQP1的小干扰RNA（siRNAs）导致AQP1显著下调，这导致PASMC迁移减少。此外，p38丝裂原活化蛋白激酶（p38-MAPK）途径的抑制消除了AQP1依赖性PASMC迁移。总之，本研究表明，AQP1通过p38-MAPK途径增强了HPS大鼠的PASMC迁移，并且可能代表了与HPS相关的肺血管重塑情况下的一种潜在治疗策略。
