Involvement of chloride channels in TGF-β1-induced apoptosis of human bronchial epithelial cells

Gang Cheng, Zhifei Shao, Bharti Chaudhari, Devendra K. Agrawal

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Abstract

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)-β. Recent growing evidence suggests that chloride (Cl -) channels are critical to cell apoptosis. We examined the effects of TGF-β1 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-β1 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-β1. siRNA for CLC-3 abolished Cl - current and enhanced TGF-β1-induced cell apoptosis. Overexpression of CLC-3 in HBECs inhibited TGF-β1-induced cell apoptosis. Bcl-2 was also downregulated after TGF-β stimulation. TGF-β1-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-β-induced apoptosis of human airway epithelial cells.

Original languageEnglish
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume293
Issue number5
DOIs
Publication statusPublished - Nov 2007

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All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

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