Involvement of chloride channels in TGF-β1-induced apoptosis of human bronchial epithelial cells
Involvement of chloride channels in TGF-β1-induced apoptosis of human bronchial epithelial cells
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DOI：
10.1152/ajplung.00121.2007
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发表时间：
2007-11-01
影响因子：
4.9
通讯作者：
Agrawal, Devendra K.
中科院分区：
文献类型：
--
作者：
Cheng, Gang;Shao, Zhifei;Agrawal, Devendra K.
气道上皮的广泛损伤和上皮修复缺陷是慢性哮喘的特征。生长因子和细胞因子在空间和时间上调控上皮细胞的脱落和修复。在这种情况下，转化生长因子(TGF)- β发挥了关键作用。最近越来越多的证据表明，氯离子（Cl-）通道对细胞凋亡至关重要。我们研究了tgf - β 1对人支气管上皮细胞（HBECs） Cl-通道表达和活性的影响及其与凋亡的关系。小干扰RNA （siRNA）方法用于研究CLC-3在HBECs细胞凋亡中的潜在作用，CLC-3是体积调节Cl-通道家族的一员。tgf - β 1显著诱导HBEC细胞凋亡，这与内源性CLC-3蛋白表达和mRNA转录物的显著降低是平行的。tgf - β 1可减弱HBECs的外向整流和电压依赖性clc -3样Cl-电流。CLC-3的siRNA可消除Cl-电流并增强tgf - β 1诱导的细胞凋亡。在HBECs中过表达CLC-3可抑制tgf - β 1诱导的细胞凋亡。tgf -刺激后Bcl-2也下调。tgf - β 1诱导的细胞凋亡在bcl -2转染的HBECs中受到抑制。我们的数据表明，clc -3样电压门控氯离子通道在tgf - β诱导的人气道上皮细胞凋亡中起关键作用。
Widespread damage of airway epithelium and defective epithelial repair are hallmarks of chronic asthma. Growth factors and cytokines spatially and temporally regulate epithelial shedding and repair. Within this context, a key function is exerted by transforming growth factor (TGF)-beta. Recent growing evidence suggests that chloride (Cl-) channels are critical to cell apoptosis. We examined the effects of TGF-beta 1 on Cl- channel expression and activity and its relationship with apoptosis in human bronchial epithelial cells (HBECs). The small interfering RNA (siRNA) approach was used to investigate the potential role of CLC-3, a member of the volume-regulated Cl- channel family, in apoptosis of HBECs. TGF-beta 1 significantly induced HBEC apoptosis, which paralleled to a significant decrease in the endogenous expression of CLC-3 protein and mRNA transcripts. Outward rectifying and voltage-dependent CLC-3-like Cl- currents in HBECs were diminished by TGF-beta 1. siRNA for CLC-3 abolished Cl- current and enhanced TGF-beta 1- induced cell apoptosis. Overexpression of CLC-3 in HBECs inhibited TGF-beta 1- induced cell apoptosis. Bcl-2 was also downregulated after TGF-beta stimulation. TGF-beta 1-induced cell apoptosis was suppressed in Bcl-2-transfected HBECs. Our data demonstrate that CLC-3-like voltage-gated chloride channels play a critical role in TGF-beta-induced apoptosis of human airway epithelial cells.