Hsa-miR-31-3p targets CLDN8 to compromise skin barrier integrity in psoriasis.

Skin barrier dysfunction in psoriasis has emerged as a significant concern, yet the underlying molecular mechanisms remain incompletely understood. This study investigates the role of hsa-miR-31-3p in regulating skin barrier function through its interaction with claudin-8 (CLDN8) in psoriasis. Through analysis of clinical samples and public datasets, we observed significantly impaired skin barrier function in psoriasis patients, characterized by increased transepidermal water loss and decreased stratum corneum hydration. Notably, CLDN8 expression was markedly downregulated in psoriatic lesions, while hsa-miR-31-3p levels were elevated. Bioinformatics analysis and molecular studies revealed that hsa-miR-31-3p directly targets the 3'UTR of CLDN8, leading to its downregulation. In vitro experiments demonstrated that both CLDN8 knockdown and hsa-miR-31-3p overexpression compromised the permeability barrier in keratinocytes. Furthermore, in an imiquimod-induced psoriasis mouse model, administration of mmu-miR-31-3p antagomir effectively ameliorated skin barrier damage, reduced inflammatory manifestations, and restored CLDN8 expression. These findings unveil a novel mechanism whereby hsa-miR-31-3p regulates skin barrier function through CLDN8 in psoriasis, suggesting potential therapeutic strategies targeting this pathway for psoriasis treatment.