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

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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
StatePublished - Nov 2007

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Chloride Channels
Transforming Growth Factors
Epithelial Cells
Apoptosis
Small Interfering RNA
Chlorides
Intercellular Signaling Peptides and Proteins
Down-Regulation
Asthma
Epithelium
Cytokines
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology

Cite this

Involvement of chloride channels in TGF-β1-induced apoptosis of human bronchial epithelial cells. / Cheng, Gang; Shao, Zhifei; Chaudhari, Bharti; Agrawal, Devendra K.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 293, No. 5, 11.2007.

Research output: Contribution to journalArticle

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