The main goal of this investigation is to find out how solute carrier family 27 member 3 (SLC27A3) is expressed in the lung tissue of mice with chronic obstructive pulmonary disease (COPD), and how it relates to lung function. A model of COPD was established by exposing organisms to cigarette smoke, followed by investigating the role of SLC27A3 in COPD through experiments conducted both in living organisms and in laboratory settings. Knockout mice lacking SLC27A3 were produced through siRNA transfection to investigate lung function and inflammatory response, using methods such as hematoxylin-eosin staining and enzyme-linked immunosorbent assay. Western blotting was carried out to analyze the expression of SLC27A3. Naïve CD4+ T-cells were stimulated with anti-CD3, anti-CD28, transforming growth factor (TGF)-β, and/or interleukin (IL)-6, and their differentiation into Th17 or Treg cells was promoted, as assessed by flow cytometry. The pathway expression of JAK2/STAT3 was detected using Western blotting. Mice with COPD that had higher expression levels of SLC27A3 in their lung tissue display abnormalities in lung architecture and function, as well as an imbalance between Th17 and Tregs and an elevated inflammatory response. In COPD mice with SLC27A3 knockdown, the JAK2/STAT3 pathway was repressed, lung inflammation was decreased, Th17/Treg balance was improved, and lung functioning was improved. In conclusion, the findings of this study suggest that downregulating SLC27A3 has the potential to attenuate the inflammatory response, mitigate COPD progression, and rebalance the Th17/Treg ratio by inhibiting the JAK2/STAT3 signaling pathway. These results lay a foundation for utilizing SLC27A3 as a potential therapeutic target to modulate the JAK2/STAT3 pathway for the treatment of COPD, with the aim of enhancing lung function, reducing inflammation, and restoring Th17/Treg equilibrium in a clinical context.
Keywords: JAK2/STAT3; Th17/Treg balance; chronic obstructive pulmonary disease; cigarette smoke; inflammatory response; solute carrier family 27 member 3.