Department of Respiratory and Critical Care Medicine, Suining Central Hospital, Suining, Sichuan, 629000, People' s Republic of China.
Department of Oral and Maxillofacial Surgery, Suining Central Hospital, Suining, Sichuan, 629000, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2023 Aug 25;18:1837-1851. doi: 10.2147/COPD.S419828. eCollection 2023.
Increased airway resistance and hyperinflation in chronic obstructive pulmonary disease (COPD) are associated with increased mechanical stress that modulate many essential pathophysiological functions including airway remodeling and inflammation. Our present study aimed to investigate the role of transient receptor potential canonical 1 (TRPC1), a mechanosensitive cation channel in airway remodeling and inflammation in COPD and the effect of glucocorticoid on this process.
In patients, we investigated the effect of pathological high mechanical stress on the expression of airway remodeling-related cytokines transforming growth factor β1 (TGF-β1), matrix metalloproteinase-9 (MMP9) and the count of inflammatory cells in endotracheal aspirates (ETAs) by means of different levels of peak inspiratory pressure (PIP) under mechanical ventilation, and analyzed their correlation with TRPC1. Based on whether patients regularly used inhaled corticosteroid (ICS), COPD patients were further divided into ICS group (n = 12) and non-ICS group (n=15). The ICS effect on the expression of TRPC1 was detected by Western blot. In vitro, we imitated the mechanical stress using cyclic stretch and examined the levels of TGF-β1 and MMP-9. The role of TRPC1 was further explored by siRNA transfection and dexamethasone administration.
Our results revealed that the TRPC1 level and the inflammatory cells counts were significantly higher in COPD group. After mechanical ventilation, the expression of TGF-β1 and MMP-9 in all COPD subgroups was significantly increased, while in the control group, only high PIP subgroup increased. Meanwhile, TRPC1 expression was positively correlated with the counts of inflammatory cells and the levels of TGF-β and MMP-9. In vitro, mechanical stretch significantly increased TGF-β1 and MMP-9 levels and such increase was greatly attenuated by TRPC1 siRNA transfection and dexamethasone administration.
Our results suggest that the increased TRPC1 may play a role in the airway inflammation and airway remodeling in COPD under high airway pressure. Glucocorticoid could in some degree alleviate airway remodeling via inhibition of TRPC1.
在慢性阻塞性肺疾病（COPD）中，气道阻力增加和过度充气与增加的机械应激有关，这种机械应激调节许多基本的病理生理功能，包括气道重塑和炎症。本研究旨在探讨机械敏感阳离子通道瞬时受体电位经典型 1（TRPC1）在 COPD 气道重塑和炎症中的作用，以及糖皮质激素对这一过程的影响。
通过机械通气时不同水平的吸气峰压（PIP），在患者中研究病理性高机械应激对气道重塑相关细胞因子转化生长因子β1（TGF-β1）、基质金属蛋白酶 9（MMP9）和支气管肺泡灌洗液（BALF）中炎症细胞计数表达的影响，并分析它们与 TRPC1 的相关性。根据患者是否定期使用吸入性糖皮质激素（ICS），将 COPD 患者进一步分为 ICS 组（n=12）和非 ICS 组（n=15）。通过 Western blot 检测 ICS 对 TRPC1 表达的影响。在体外，我们通过循环拉伸模拟机械应激，并检测 TGF-β1 和 MMP-9 的水平。通过 siRNA 转染和地塞米松给药进一步探讨 TRPC1 的作用。
我们的结果表明，TRPC1 水平和炎症细胞计数在 COPD 组中明显更高。机械通气后，所有 COPD 亚组的 TGF-β1 和 MMP-9 表达均明显增加，而对照组仅高 PIP 亚组增加。同时，TRPC1 表达与炎症细胞计数以及 TGF-β 和 MMP-9 的水平呈正相关。在体外，机械拉伸显著增加了 TGF-β1 和 MMP-9 的水平，而 TRPC1 siRNA 转染和地塞米松给药大大减弱了这种增加。
我们的结果表明，在高气道压力下，TRPC1 的增加可能在 COPD 中的气道炎症和气道重塑中起作用。糖皮质激素通过抑制 TRPC1 在一定程度上缓解气道重塑。
