ClC-3 chloride channel is upregulated by hypertrophy and inflammation in rat and canine pulmonary artery
ClC-3 chloride channel is upregulated by hypertrophy and inflammation in rat and canine pulmonary artery
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DOI：
10.1038/sj.bjp.0706135
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发表时间：
2005-05-01
影响因子：
7.3
通讯作者：
Yamboliev, IA
中科院分区：
文献类型：
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作者：
Dai, YP;Bongalon, S;Yamboliev, IA
1氯离子通道参与细胞的体积调节、细胞周期进展、细胞增殖和收缩等基本功能，但对ClC-3通道的生理功能存在争议。我们验证了野百合碱处理的大鼠高血压时ClC-3基因(CLCN-3)上调的假说，以及上调ClC-3通道辅助肺动脉平滑肌细胞(PASMC)活性的假说。2单次皮下注射野百合碱(60 mg kg(-1))诱导大鼠实验性肺动脉高压。3逆转录-聚合酶链式反应(RT-PCR)、免疫组织化学和免疫印迹分析表明，组织病理学改变与高血压肺血管平滑肌细胞和心肌细胞ClC-3mRNA和蛋白表达上调有关。4对犬PASMCs提取的mRNA进行RT-PCR分析表明，与炎症介质内皮素-1(ET-1)、血小板衍生生长因子(PDGF)、白介素1β(IL-1β)和肿瘤坏死因子α(TNFα)共同孵育，5腺病毒介导的ClC-3在犬PASMCs中的高表达和提高了细胞活力，以对抗过氧化氢(H_2O_2，范围50-250µM)浓度的增加。6综上所述，CLC-3在高血压大鼠肺和心脏中的上调是一个新的观察结果。我们的功能数据表明，ClC-3的上调是炎症的肺动脉的一种适应性反应，它增强了PASMCs对活性氧的生存能力。
1 Cl- channels have been implicated in essential cellular functions including volume regulation, progression of cell cycle, cell proliferation and contraction, but the physiological functions of the ClC-3 channel are controversial. We tested the hypothesis that the ClC-3 gene (ClCn-3) is upregulated in hypertensive pulmonary arteries of monocrotaline-treated rats, and upregulated ClC-3 channel aids viability of pulmonary artery smooth muscle cells (PASMCs).2 Experimental pulmonary hypertension was induced in rats by a single subcutaneous administration of monocrotaline (60 mg kg(-1)). Injected animals developed characteristic features of pulmonary hypertension including medial hypertrophy of pulmonary arteries and right ventricular hypertrophy.3 Reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry and Western immunoblot analysis indicated that histopathological alterations were associated with upregulation of the ClC-3 mRNA and protein expression in both smooth muscle cells of hypertensive pulmonary arteries and in cardiac myocytes.4 RT-PCR analysis of mRNA, extracted from canine cultured PASMCs, indicated that incubation with the inflammatory mediators endothelin-1 (ET-1), platelet-derived growth factor (PDGF), interleukin-1beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha), but not transforming growth factor beta (TGF beta), upregulated ClC-3 mRNA.5 Adenovirus-mediated delivery and overexpression of ClC-3 in canine PASMCs improved cell viability against increasing concentrations of hydrogen peroxide (H2O2, range 50-250 mu M).6 In conclusion, upregulation of ClC-3 in rat hypertensive lung and heart is a novel observation. Our functional data suggest that upregulation of ClC-3 is an adaptive response of inflamed pulmonary artery, which enhances the viability of PASMCs against reactive oxygen species.