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Role of TRPC1 channels in pressure-mediated activation of airway remodeling
- Source :
- Respiratory Research, Respiratory Research, Vol 20, Iss 1, Pp 1-12 (2019)
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
Abstract
- Background Bronchoconstriction and cough, a characteristic of the asthmatic response, leads to development of compressive stresses in the airway wall. We hypothesized that progressively pathological high mechanical stress could act on mechanosensitive cation channels, such as transient receptor potential channel 1 (TRPC1) and then contributes to airway remodeling. Methods We imitate the pathological airway pressure in vitro using cyclic stretch at 10 and 15% elongation. Ca2+ imaging was applied to measure the activity of TRPC1 after bronchial epithelial cells exposed to cyclic stretch for 0, 0.5, 1, 1.5, 2, 2.5 h. To further clarify the function of channnel TRPC1 in the process of mechano-transduction in airway remodeling, the experiment in vivo was implemented. The TRPC1 siRNA and budesonide were applied separately to asthmatic models. The morphological changes were measured by HE and Massion method. The expression levels of TRPC1 were evaluated by real-time PCR, western blot and immunohistochemistry. The protein expression level of IL-13, TGF-β1 and MMP-9 in BALF were measured by ELISA. Results The result showed that cyclic stretch for 15% elongation at 1.5 h could maximize the activity of TRPC1 channel. This influx in Ca2+ was blocked by TRPC1 siRNA. Higher TRPC1 expression was observed in the bronchial epithelial layer of ovalbumin induced asthmatic models. The knockdown of TRPC1 with TRPC1 siRNA was associated with a hampered airway remodeling process, such as decreased bronchial wall thickness and smooth muscle hypertrophy/hyperplasia, a decreased ECM deposition area and inflammation infiltration around airway wall. Meantime, expression of IL-13, TGF-β1 and MMP-9 in OVA+TRPC1 siRNA also showed reduced level. TRPC1 intervention treatment showed similar anti-remodeling therapeutic effect with budesonide. Conclusions These results demonstrate that most TRPC1 channels expressed in bronchial epithelial cells mediate the mechanotransduction mechanism. TRPC1 inducing abnormal Ca2+ signal mediates receptor-stimulated and mechanical stimulus-induced airway remodeling. The inhibition of TRPC1 channel could produce similar therapeutic effect as glucocortisteroid to curb the development of asthmatic airway remodeling.
- Subjects :
- Male
0301 basic medicine
TRPC1 channel
Ovalbumin
Guinea Pigs
Mechanotransduction, Cellular
TRPC1
03 medical and health sciences
Transient receptor potential channel
0302 clinical medicine
Pressure
medicine
Animals
Humans
Calcium Signaling
Mechanotransduction
Lung
Cells, Cultured
TRPC Cation Channels
lcsh:RC705-779
biology
Chemistry
Research
lcsh:Diseases of the respiratory system
Airway remodeling
respiratory system
Asthma
Cell biology
Ca2+
030104 developmental biology
030228 respiratory system
Asthmatic Airway Remodeling
biology.protein
Bronchoconstriction
Mechanosensitive channels
Smooth muscle hypertrophy
medicine.symptom
Subjects
Details
- ISSN :
- 1465993X
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- Respiratory Research
- Accession number :
- edsair.doi.dedup.....3d579f508fe89b5f6374d23b974c2dcf