The involvement of aquaporin 1 in the hepatopulmonary syndrome rat serum-induced migration of pulmonary arterial smooth muscle cells via the p38-MAPK pathway
The involvement of aquaporin 1 in the hepatopulmonary syndrome rat serum-induced migration of pulmonary arterial smooth muscle cells via the p38-MAPK pathway
复制标题
水通道蛋白 1 通过 p38-MAPK 途径参与肝肺综合征大鼠血清诱导的肺动脉平滑肌细胞迁移。
DOI：
10.1039/c5mb00347d
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发表时间：
2015-01-01
影响因子：
--
通讯作者：
Yi, Bin
中科院分区：
文献类型：
--
作者：
Gao, Jing;Chen, Lin;Yi, Bin
肝硬化综合征（HPS）是以肺内血管扩张（IPVD）引起的动脉氧合障碍为特征的疾病。肺血管重构（PVR）是IPVD的重要病理特征;然而，关于该过程的潜在机制的细节仍不明确。近年来的研究表明，肺动脉平滑肌细胞（PASMCs）的异常迁移在HPS相关PVR的发病机制中起一定作用。此外，水通道蛋白1（AQP 1）不仅作为一个水通道分子，而且还通过促进迁移细胞的板状伪足中的水运输来促进细胞迁移。胆总管结扎（CBDL）大鼠是公认的HPS模型，我们确定AQP 1的免疫过氧化物酶标记在CBDL大鼠肺血管中膜增强。HPS大鼠血清介导PASMC中AQP 1的过度表达，并上调PASMC的迁移。针对大鼠AQP 1的小干扰RNA（siRNA）引起AQP 1的显著下调，从而导致PASMC迁移减少。此外，p38-MAPK通路的抑制消除了AQP 1依赖的PASMC迁移。总之，本研究表明，AQP 1通过p38-MAPK途径增强了HPS大鼠PASMC的迁移，并可能代表了与HPS相关的肺血管重建的潜在治疗策略。
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.