AQP1促进肺动脉平滑肌细胞的增殖与迁移  

The Aquaporin 1 Protein Promotes Migration and Proliferation of Pulmonary Arterial Smooth Muscle Cells

作　　者：赖宁[1] 钟典 云昕[1] 金颖康[1] 

机构地区：[1]呼吸疾病国家重点实验室广州呼吸疾病研究所广州医科大学附属第一医院呼吸内科,广州510120

出　　处：《中国生物化学与分子生物学报》2017年第7期697-705,共9页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金(No.81500046);广东省自然科学基金(No.2014A030310016);广州市教育局科研项目(No.1201430156);广州市科技创新委员会科研项目(No.201607010356);广东省教育厅科研项目(No.2015KQNCX130)资助~~

摘　　要：肺动脉平滑肌细胞(PASMCs)的迁移和增殖是肺动脉重塑进而造成肺动脉高压的主要病理基础。水通道蛋白1(AQP1)具有促进上皮细胞、内皮细胞迁移的作用,但机制不清。由于AQP1也表达于血管平滑肌细胞,推测AQP1可能参与缺氧诱导的PASMCs增殖及迁移。通过PCR和免疫印迹分析,检测AQP的表达以及缺氧对AQP表达水平的影响,并通过细胞迁移以及增殖实验观察AQP1在缺氧诱导的PASMCs迁移与增殖中的作用。AQP1在PASMCs和主动脉平滑肌细胞(Ao SMCs)均表达,但缺氧只增加PASMCs中AQP1的表达,以及促进PASMCs的迁移与增殖。敲除AQP1可抑制PASMCs的增殖以及缺氧诱导的细胞增殖和迁移。过表达AQP1促进PASMCs的增殖和迁移。缺氧促进β联蛋白在PASMCs内的表达。敲除β联蛋白后,抑制Ad AQP1所介导的PASMCs迁移与增殖。这些结果表明,缺氧可促进AQP1在肺动脉内的表达,AQP1可通过β联蛋白对PASMCs的增殖和迁移进行调节。Prolonged exposure to hypoxia adversely affects the pulmonary vasculature,decreases luminal diameters of the pulmonary arteries due to contraction and vascular remodeling,and results in pulmonary hypertension. Vascular remodeling under hypoxic conditions is partly due to proliferation and migration of pulmonary arterial smooth muscle cells（ PASMCs）. Aquaporin 1（ AQP1） was the first identified aquaporin family member and has been demonstrated to aid in migration of epithelial,endothelial,smooth muscle and some tumor cells,but the mechanism remains unclear. Since AQP1 is expressed in some types of vascular smooth muscles,we found that AQP1 was abundant in both PASMCs and aortic smooth muscle cells（ Ao SMCs） with immunoblotting and PCR techniques. Moreover,hypoxia increased AQP1 protein levels,as well as migration and proliferation of PASMCs. Knockdown of AQP1 reduced basal proliferation,hypoxia-induced migration and proliferation of PASMCs, while AQP1 overexpressionincreased PASMC migration and proliferation. Mechanistically,hypoxia increased β-catenin protein levels in PASMCs. Depletion of β-catenin prevented the increase of AQP1-induced migration and proliferation. Our results suggest that hypoxia increased AQP1 protein levels in rat pulmonary arteries,and AQP1 mediates migration and proliferation of PASMCs via β-catenin.

关 键 词：水通道蛋白1 肺动脉平滑肌细胞 缺氧 

分 类 号：R322[医药卫生—人体解剖和组织胚胎学]