Abstract:

Objective: To explore the expression of pressure-sensitive transient receptor potential channel (TRPC1) in bronchial epithelium cells of the patients with chronic obstructive pulmonary disease(COPD), and to explain the molecular mechanism about the participation of TRPC1 in airway remodeling.Methods: Sixty-four patients who needed fiberoptic bronchoscope for diagnosis were selected.All the patients were used as non-operation group and divided into COPD group(40 cases of mild to moderate grade) and control group(24 cases without chronic airway inflammatory disease) according to Respiratory Disease Guideline.The level of the forced expiatory volume/forced vital capacity (FEV₁/FVC) in the first second and forced expiatory volume in the first second of the expected value (FEV₁% pred) were detected by lung function test.The expression levels of TRPC1, matrix metalloproteinase(MMP-9) and transforming growth factor-β₁(TGF-β₁) in bronchoalveolar liquid(BALF) were measured by ELISA.The relevance among expression level of TRPC1 and levels of FEV₁/FVC, FEV₁% pred, MMP-9, TGF-β1 was analyzed.Seventeen lung samples from the patients underwent pulmonary lobectomy were selected. All the patients were used as operation group and divided into COPD group(8 cases of mild to moderate grade) and control group(9 cases without chronic airway inflammatory disease). Then indictator relevance to airway remodeling, such as thickness-diameter ratio(TDR%), percentage of wall thickness(WA%) were measured.The immunohistochemistry experiment was used to detect the distribution characteristics of TRPC1 protein in human bronchial epithelial cells.The Imagepro-plus 6.0 software was used to analyze the expression difference of TRPC1 protein between COPD and control groups.Western blotting method was used to detect the expression level of TRPC1.The correlation between the expression level of TRPC1 and TDR%, WA% was analyzed.Results: The lung function detection results showed that in non-operation group, the levels of FEV₁% pred and FEV₁/FVC in COPD group were decreased compared with control group(P<0.05).The expression levels of TRPC1, MMP-9 and TGF-β1 in COPD group were increased compared with control group(P<0.05). The expression level of TRPC1 was negatively correlated with FEV₁%pred(r=-0.34, P=0.002) and FEV1/FVC(r=-0.38, P=0.004).The expression level of TRPC1 was positively correlated with MMP-9(r=0.36, P=0.004) and TGF-β₁ (r=0.61, P=0.002).The immunohistochemistry results in operation group displayed that the TRPC1 protein was mainly distributed in the epithelial columnar cell nucleus and the cell membrane near lumen within the bronchial epithelium.The ratio of integrated optical density(IOD) to area within the bronchial epithelium in COPD group was significantly higher than that in control group(P<0.05).The expression level of TRPC1 protein detected by Western blotting method in COPD group was higher than that in control group(P<0.05).The expression level of TRPC1 was positively correlated with TDR%(r=0.59, P=0.002) and WA%(r=0.60, P=0.002).Conclusion: The TRPC1 channel in human bronchial epithelial cells of COPD patients is actived and up-regulated.The expression level of TRPC1 channel is positively correlated with impared extent of lung function and the expression levels of cytokines relevant to airway remodeling.All above imply that pressure-sensitive TRPC1 channel could promote the development of airway remodeling.

Key words: chronic obstructive pulmonary disease, transient receptor potential canonical 1, airway remodeling