Proteomic and experimental analyses reveal molecular signatures of flexural atopic dermatitis in antecubital and popliteal fossae and the therapeutic effect of Aida lotion

Introduction The mechanisms underlying the predilection of atopic dermatitis for the antecubital and popliteal fossae remain unexplored. This preliminary exploratory study aimed to characterize the proteomic features of typical flexural atopic dermatitis lesions using proteomics integrated with animal model validation and to clarify the therapeutic mechanisms of Aida lotion. Methods We recruited five patients with atopic dermatitis. Skin scale samples were collected from the flexural side of the antecubital and popliteal areas as the observation group, while samples from the corresponding extensor sides were used as the control group. Stratum corneum specimens were analyzed using ultra-sensitive proteomic techniques and bioinformatics to screen for differentially expressed proteins. Key candidate proteins were then validated in an atopic dermatitis mouse model to further explore the therapeutic mechanisms of Aida lotion. Results A total of 712 differential proteins were identified. GO analysis indicated enrichment in pathways related to DNA replication, proteasome regulation, and myosin V binding. KEGG pathway analysis highlighted the importance of the PPAR and MAPK signaling pathways in the site-specific prevalence of atopic dermatitis. Key differentially expressed proteins including CYP27A1, CPT1A, FABP5 in the PPAR pathway and MAP2K3, MAP2K1, HRAS in the MAPK pathway, showed the highest fold changes. Animal experiments showed that atopic dermatitis induction increased SCORAD scores, edema, and inflammatory infiltration. Additionally, the expression levels of CPT1A, FABP5, MAP2K3, MAP2K1, and HRAS were upregulated, whereas the expression of CYP27A1 was downregulated, which was consistent with the proteomic findings, indicating that these targets have been validated as key proteins associated with the molecular pathology of flexural atopic dermatitis lesions in antecubital and popliteal fossa regions. Treatment with Aida lotion reversed these changes by downregulating CPT1A, FABP5, MAP2K3, MAP2K1, and HRAS, and upregulating CYP27A1, thereby alleviating dermatitis symptoms and reducing inflammatory and mast cell infiltration. Discussion These findings identify CYP27A1, CPT1A, FABP5, MAP2K3, MAP2K1, and HRAS are prominent molecular signatures of atopic dermatitis in the antecubital and popliteal fossae. Aida lotion exerts therapeutic effects by modulating these key proteins and associated pathways.