瞬时受体电位通道蛋白1（TRPC1）对慢性阻塞性肺疾病患者气道上皮-间质转化的影响
Effects of TRPC1 on epithelial mesenchymal transition in human airway in chronic obstructive pulmonary disease.
作者信息
Xu Feng, Liu Xiao-Chun, Li Li, Ma Chao-Nan, Zhang Ya-Jun
机构信息
Department of Respiration, Huaihe Hospital of Henan University College of Nursing and Health, Henan University, Kaifeng, P.R. China.
出版信息
Medicine (Baltimore). 2017 Oct;96(43):e8166. doi: 10.1097/MD.0000000000008166.
BACKGROUND
We investigated the effects of TRPC1 on epithelial mesenchymal transition (EMT) in human airway in chronic obstructive pulmonary disease (COPD).
METHODS
A total of 94 patients who underwent lobectomy were selected and divided into COPD (49 cases) and control (45 cases) groups. Immunohistochemistry was applied to detect expression of E-cadherin and vimentin and TRPC1. Correlation of TRPC1 expression with E-cadherin and vimentin expression, and correlations of lung function indicators in COPD patients with expression of TRPC1, E-cadherin, and vimentin were analyzed. Human airway epithelial cells (16HBE) were used for cell experiments; and cigarette smoking extract (CSE) was adopted to establish the COPD model using TRPC1 recombinant plasmids and siRNA. Cells were assigned into the control, CSE, CSE + vector, CSE + TRPC1, CSE + si-NC, and CSE + si-TRPC1 groups. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were implemented to detect expression of TRPC1, E-cadherin, and vimentin.
RESULTS
Compared with the control group, expression of TRPC1 and vimentin significantly increased while expression of E-cadherin decreased in the COPD group, and protein expression of TRPC1 was positively correlated with the protein expression of vimentin but negatively correlated with the protein expression of E-cadherin. Patients exhibiting positive expression of TRPC1 had lower FEV1, FEV1%Pred, and FEV1/FVC, compared with the patients exhibiting negative expression of TRPC1. Compared with the control group, expression of TRPC1 and vimentin increased, whereas expression of E-cadherin decreased in the CSE, CSE + vector, CSE + TRPC1, and CSE + si-NC groups. Compared with the CSE and CSE + vector groups, the expression of TRPC1 and vimentin increased but the expression of E-cadherin decreased in the CSE + TRPC1 group. Compared with the CSE and CSE + si-NC groups, the expression of TRPC1 and vimentin decreased but the expression of E-cadherin increased in the CSE + si-TRPC1 group. No significant differences were observed among the CSE, CSE + vector and CSE + si-NC groups.
CONCLUSION
Overexpression of TRPC1 in COPD promoted EMT process and TRPC1 may be a new and interesting focus for COPD new treatment in the future.
背景
我们研究了瞬时受体电位通道蛋白1（TRPC1）对慢性阻塞性肺疾病（COPD）患者气道上皮-间质转化（EMT）的影响。
方法
选取94例行肺叶切除术的患者，分为COPD组（49例）和对照组（45例）。采用免疫组织化学法检测E-钙黏蛋白、波形蛋白和TRPC1的表达。分析TRPC1表达与E-钙黏蛋白和波形蛋白表达的相关性，以及COPD患者肺功能指标与TRPC1、E-钙黏蛋白和波形蛋白表达的相关性。用人气道上皮细胞（16HBE）进行细胞实验；采用香烟烟雾提取物（CSE），利用TRPC1重组质粒和小干扰RNA（siRNA）建立COPD模型。将细胞分为对照组、CSE组、CSE+载体组、CSE+TRPC1组、CSE+si-NC组和CSE+si-TRPC1组。采用定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹法检测TRPC1、E-钙黏蛋白和波形蛋白的表达。
结果
与对照组相比，COPD组TRPC1和波形蛋白表达显著增加，而E-钙黏蛋白表达降低，且TRPC1蛋白表达与波形蛋白蛋白表达呈正相关，与E-钙黏蛋白蛋白表达呈负相关。TRPC1表达阳性的患者，其第1秒用力呼气容积（FEV1）、FEV1占预计值百分比（FEV1%Pred）和FEV1/用力肺活量（FVC）低于TRPC1表达阴性的患者。与对照组相比，CSE组、CSE+载体组、CSE+TRPC1组和CSE+si-NC组TRPC1和波形蛋白表达增加，而E-钙黏蛋白表达降低。与CSE组和CSE+载体组相比，CSE+TRPC1组TRPC1和波形蛋白表达增加，而E-钙黏蛋白表达降低。与CSE组和CSE+si-NC组相比，CSE+si-TRPC1组TRPC1和波形蛋白表达降低，而E-钙黏蛋白表达增加。CSE组、CSE+载体组和CSE+si-NC组之间未观察到显著差异。
结论
COPD中TRPC1的过表达促进了EMT进程，TRPC1可能是未来COPD新治疗的一个新的且有趣的靶点。
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