Elevated Urotensin-II and TGF-β Levels in COPD: Biomarkers of Fibrosis and Airway Remodeling in Smokers

Abstract

Background and Objectives: Small airway fibrosis plays a critical role in the progression of chronic obstructive pulmonary disease (COPD). Previous research has suggested that Urotensin-II (U-II) and transforming growth factor-β (TGF-β) may contribute to pathological fibrosis in various organs, including the cardiovascular system, lungs, and liver. However, their specific relationship with airway fibrosis in COPD has not yet been thoroughly investigated. This study aims to evaluate the concentrations of U-II and TGF-β in individuals with COPD, as well as in healthy smokers and non-smokers, to explore their potential roles in COPD-related fibrosis. Materials and Methods: The study included three distinct groups: a healthy non-smoker control group (n = 98), a healthy smoker group (n = 78), and a COPD group (n = 80). All participants in the COPD group had a smoking history of at least 10 pack-years. COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, with only patients classified as GOLD stage 2 or higher being included in the study. Urotensin-II (U-II) and transforming growth factor-β (TGF-β) levels were measured using a commercially available ELISA kit. Results: COPD patients had a significantly lower FEV1 (58 ± 15.4%) compared to smokers (79 ± 4.5%) and non-smokers (92 ± 3.7%) (p < 0.001). Similarly, COPD patients had a lower FEV1/FVC ratio (55 ± 9.4%) compared to smokers (72 ± 4.2%) and non-smokers (85 ± 3.6%) (p < 0.01 and p < 0.05, respectively). SaO2 was significantly lower in COPD patients (87%) compared to smokers (96.5%) and non-smokers (98%) (COPD vs. smokers: p < 0.05 and smokers vs. non-smokers: p > 0.05). U-II levels were significantly higher in COPD patients (175.10 ± 62.40 pg/mL) compared to smokers (118.50 ± 45.51 pg/mL) and non-smokers (85.29 ± 35.87 pg/mL) (p < 0.001 and p < 0.05, respectively). COPD patients also had significantly higher levels of TGF-β (284.60 ± 60.50 pg/mL) compared to smokers (160.00 ± 41.80 pg/mL) and non-smokers (92.00 ± 25.00 pg/mL) (p < 0.001 and p < 0.05, respectively). Conclusions: Our study supports the growing body of evidence that U-II and TGF-β play central roles in the development and progression of fibrosis in COPD. The negative correlation between these markers and lung function parameters such as FEV1 and FEV1/FVC indicates that they may be key drivers of airway remodeling and obstruction. These biomarkers could serve as early indicators of fibrotic changes in smokers, even before the onset of COPD.