The role of LINC00114 in atopic dermatitis: modulating inflammation and epidermal barrier dysfunction

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by a dysregulated immune response and impaired epidermal barrier function. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of gene expression in various diseases, yet their specific roles in AD remain poorly understood. This study investigates the role of LINC00114, an lncRNA identified as significantly upregulated in lesional skin of AD patients. Using RNA sequencing, quantitative real-time PCR, and in vitro experiments, we demonstrate that LINC00114 is induced by Th2 cytokines IL-4 and IL-13, correlating with clinical severity scores. Notably, the observed 2–3 fold changes in LINC00114 expression indicate a substantial biological impact; as such alterations can significantly influence inflammatory pathways and epidermal barrier integrity. Mechanistically, LINC00114 functions as a molecular sponge for miR-128, inhibiting its regulatory effects on pro-inflammatory targets. Furthermore, LINC00114 enhances the JAK/STAT signaling pathway, promoting Th2-driven inflammation. Our findings also reveal that LINC00114 impairs epidermal barrier function by downregulating key proteins such as filaggrin and involucrin. In a murine model of AD, targeting LINC00114 with siRNA significantly reduced skin inflammation and improved barrier integrity. These results highlight LINC00114 as a novel therapeutic target for AD, offering potential avenues for more effective treatments aimed at restoring immune balance and skin barrier function.