Transcriptional dysregulation of skin barrier genes in atopic dermatitis and psoriasis: Mechanistic insights and emerging therapeutic strategies

Skin barrier dysfunction plays a pivotal role in the pathogenesis of inflammatory skin diseases such as atopic dermatitis and psoriasis. This review provides a comprehensive analysis of recent advances in the transcriptional and post-transcriptional regulation of key skin barrier-related genes, including FLG, LOR, CLDN1, AQP3 and IVL. We detail how intrinsic genetic variations and immune-mediated cytokine pathways-particularly the T helper 2 and T helper 17 axes-disrupt the epidermal defense system. Emerging therapeutic strategies targeting skin barrier restoration through natural compounds, biologic agents, and gene modulation technologies-such as small interfering RNA, antisense oligonucleotides, and histone deacetylase inhibitors-are critically reviewed. Moreover, the impact of the gut-skin axis and microbial metabolites on epidermal gene expression is discussed. Finally, we highlight the role of artificial intelligence and multi-omic integration in driving biomarker discovery and enabling precision dermatology. These insights underscore the potential of barrier-centric, gene-targeted approaches as a transformative strategy in managing chronic dermatoses.