The DSG1-AS1/miR-125b-5p/HMGA2 axis is associated with the formation of neutrophil extracellular traps in atopic dermatitis.

BACKGROUND

As a chronic inflammatory skin disease, atopic dermatitis (AD) results from immune dysregulation, epidermal barrier dysfunction, and inflammatory microenvironment. Although long non-coding RNAs (lncRNAs) and neutrophil extracellular traps (NETs) are implicated in inflammatory diseases, the role of the DSG1-AS1/miR-125b-5p/HMGA2 axis in AD and its link to NETs formation remain unclear.

OBJECTIVE

This research sought to explore the role of the DSG1-AS1/miR-125b-5p/HMGA2 axis in AD pathogenesis, focusing on its regulation of keratinocyte inflammation, neutrophil recruitment, and NETs formation, and evaluate its potential as a diagnostic biomarker.

METHODS

The expression levels of DSG1-AS1, miR-125b-5p and HMGA2 were detected by real-time quantitative PCR (RT-qPCR). Molecular interactions were validated by dual-luciferase reporter assay. Cell migration was assessed using Transwell co-culture. NET markers were detected by ELISA. Cell viability and apoptosis were measured via CCK-8 and flow cytometry. The expression of the DSG1-AS1/miR-125b-5p/HMGA2 axis in AD and its correlation with NET formation were analyzed by collecting serum samples from healthy volunteers and AD patients, and its potential value as a biomarker was evaluated by the ROC curve.

RESULTS

DSG1-AS1 upregulated HMGA2 expression by suppressing miR-125b-5p, thereby exacerbating the inflammation of human keratinocytes and promoting its recruitment of human neutrophils (hNE). Moreover, DSG1-AS1 promoted NET formation of hNE via regulation of miR-125b-5p/HMGA2, impairing keratinocyte survival. Clinically, elevated serum DSG1-AS1/HMGA2 and reduced serum miR-125b-5p positively correlated with NET formation and disease severity. The combination of these molecules showed high diagnostic accuracy in AD (AUC = 0.878).

CONCLUSION

Our findings suggest that the DSG1-AS1/miR-125b-5p/HMGA2 axis may be closely related to AD progression by regulating NET formation, potentially offering novel biomarkers and therapeutic targets based on our in vitro and clinical serum data.