Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disorder that progresses slowly and is characterized by cough, asthma, dyspnea and shortness of breath. Previous studies have shown that cigarette smoke (CS) is one of the major causes of COPD. Chronic bronchial inflammation induced by CS promotes lung injury, fibrosis and remodeling, finally leading to emphysema, a lung condition that causes shortness of breath. However, the potential mechanism of CS-mediated COPD symptoms remains incompletely understood. Therefore, researchers from the Loudi Central Hospital sought to explore the underlying mechanism and relationship between CS-induced inflammation and the development of COPD.
Sphingosine-1-phosphate (S1P) is one of the major sphingolipid metabolites synthesized by sphingosine kinases (SphKs). SphK2 is highly expressed in the lungs, but its role in COPD remains unclear. In the present study, researchers found that both mRNA and protein levels of SphK2 were significantly upregulated in mouse lungs after CS exposure for 6 months, which is closely associated with lung inflammation and fibrosis induced by CS. However, in SphK2 gene knockout mice, accumulation of neutrophils, secretion of inflammatory cytokines, and lung fibrosis induced by CS were markedly reduced. In addition, the deletion of SphK2 also rescued the expression of CFTR, which is an important protein in epithelial surface hydration, barrier function and innate defense.
This study demonstrated the crucial role of SphK2 in the pathogenesis of COPD, and it was proven that SphK2 deficiency would be beneficial for the treatment of lung inflammation, remodeling, and COPD after chronic CS exposure. Therefore, SphK2 could be an effective therapeutic target for COPD-like symptoms and diseases.
慢性阻塞性肺病 (COPD) 是一種進展緩慢的慢性呼吸系統疾病，以咳嗽、哮喘、呼吸困難和呼吸急促為特徵。以往的研究表明，香煙煙霧（CS）是導致慢性阻塞性肺病的主要原因之一。 CS 引起的慢性支氣管炎症會促進肺損傷、纖維化和重塑，最終導致肺氣腫，這是一種導致呼吸急促的肺部疾病。然而，CS 介導的 COPD 症狀的潛在機制仍不完全清楚。因此，婁底市中心醫院的研究人員試圖探索 CS 引起的炎症與 COPD 發展之間的潛在機制和關係。
1-磷酸鞘氨醇 (S1P) 是由鞘氨醇激酶 (SphKs) 合成的主要鞘脂代謝物之一。 SphK2 在肺中高度表達，但其在 COPD 中的作用仍不清楚。在本研究中，研究人員發現，CS 暴露 6 個月後，小鼠肺部 SphK2 的 mRNA 和蛋白水平均顯著上調，這與 CS 誘導的肺部炎症和纖維化密切相關。然而，在 SphK2 基因敲除小鼠中，中性粒細胞的積累、炎性細胞因子的分泌和 CS 誘導的肺纖維化顯著減少。此外，SphK2 的缺失還挽救了 CFTR 的表達，CFTR 是上皮表面水合、屏障功能和先天防禦的重要蛋白。
本研究證明了 SphK2 在 COPD 發病機制中的關鍵作用，並證明 SphK2 缺乏將有利於慢性 CS 暴露後肺部炎症、重塑和 COPD 的治療。因此，SphK2 可能是 COPD 樣症狀和疾病的有效治療靶點。
Reference: Chen Y, Zhang Y, Rao C, Huang J, Qing Q. Deletion of sphingosine kinase 2 attenuates cigarette smoke-mediated chronic obstructive pulmonary disease-like symptoms by reducing lung inflammation. Bosn J of Basic Med Sci [Internet]. 2022Oct.12 [cited 2022Oct.20];. Available from: https://www.bjbms.org/ojs/index.php/bjbms/article/view/8034
Editor: Merima Bukva, MPharm