The DSG1-AS1/miR-125b-5p/HMGA2 axis is associated with the formation of neutrophil extracellular traps in atopic
Heng Wang1, Xuefei Ke1, Xinyue Chen1
1Department of Dermatology, Taihe Hospital, Hubei University of Medicine, No. 32 South Renmin Road, Shiyan, 442099, Hubei, China.
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.
