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 language | English |
|---|---|
| Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
| Volume | 293 |
| Issue number | 5 |
| DOIs | |
| State | Published - Nov 2007 |
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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 journal › Article
}
TY - JOUR
T1 - Involvement of chloride channels in TGF-β1-induced apoptosis of human bronchial epithelial cells
AU - Cheng, Gang
AU - Shao, Zhifei
AU - Chaudhari, Bharti
AU - Agrawal, Devendra K.
PY - 2007/11
Y1 - 2007/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=36348982335&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36348982335&partnerID=8YFLogxK
U2 - 10.1152/ajplung.00121.2007
DO - 10.1152/ajplung.00121.2007
M3 - Article
C2 - 17873007
AN - SCOPUS:36348982335
VL - 293
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
SN - 1040-0605
IS - 5
ER -