PubMed 17873007

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClvC3 , ClvC4

Title: Involvement of chloride channels in TGF-beta1-induced apoptosis of human bronchial epithelial cells.

Authors: Gang Cheng, Zhifei Shao, Bharti Chaudhari, Devendra K Agrawal

Journal, date & volume: Am. J. Physiol. Lung Cell Mol. Physiol., 2007 Nov , 293, L1339-47

PubMed link:

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-beta1 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-beta1 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-beta1. siRNA for CLC-3 abolished Cl(-) current and enhanced TGF-beta1-induced cell apoptosis. Overexpression of CLC-3 in HBECs inhibited TGF-beta1-induced cell apoptosis. Bcl-2 was also downregulated after TGF-beta stimulation. TGF-beta1-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.