SULT1E1 exerts a protective role in COPD by inhibiting the AKT pathway: an in vivo and in vitro study.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory illness characterized by an irreversible pathological process that creates an urgent need for novel molecular targets for effective prevention, diagnosis, and treatment. Estrogen sulfotransferase (SULT1E1), a phase II cytoplasmic enzyme, is downregulated in various cancers and inflammatory diseases. Although its role in other conditions has been explored, its function in COPD remains unclear. This study aimed to assess SULT1E1 expression and underlying mechanisms in COPD pathogenesis. We identified differentially expressed genes by analyzing four microarray datasets (GSE10006, GSE18385, GSE29133, and GSE37768) obtained from the gene expression omnibus database. Gene ontology and Kyoto encyclopedia of genes and genomes analyses were conducted, and protein-protein interaction networks were constructed. The SULT1E1 expression was validated in clinical samples from patients with COPD (n = 92) and healthy controls (n = 40) using serum enzyme-linked immunosorbent assay and PBMC RT-qPCR, with a correlation to lung function assessed. A rat model of COPD was used to evaluate SULT1E1 protein levels in lung tissue by Western blotting and immunohistochemistry. In vitro studies modulated SULT1E1 expression in BEAS-2B cells to assess effects on cell proliferation, apoptosis, epithelial-mesenchymal transition (EMT), and AKT phosphorylation. Bioinformatic analyses revealed a significantly lower SULT1E1 expression in lung tissues of patients with COPD. Clinically, serum and PBMC SULT1E1 levels were significantly reduced in patients with COPD, exhibiting a positive correlation with lung function indicators, including FEV1% and FEV1/FVC (P < 0.001). These findings were further supported by a rat model of COPD, which demonstrated decreased SULT1E1 protein expression. In vitro studies indicated that SULT1E1 knockdown in BEAS-2B cells promoted proliferation and EMT, inhibited apoptosis, and increased AKT phosphorylation. Conversely, SULT1E1 overexpression led to opposing effects, inhibiting proliferation and EMT; however, it also promoted apoptosis and reduced AKT phosphorylation. Our findings demonstrate that low SULT1E1 expression is a key characteristic of COPD and correlates with disease severity. SULT1E1 appears to play a protective role by regulating AKT phosphorylation, thereby influencing cell proliferation, apoptosis, and EMT. These results identify SULT1E1 as a potential prognostic biomarker and a novel therapeutic target for COPD.