Sp1-mediated miR-193b suppresses atopic dermatitis by regulating HMGB1.

Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease. Keratinocyte dysfunction plays a central role in AD development. MicroRNA is a novel player in many inflammatory and immune skin diseases. In this study, we investigated the potential function and regulatory mechanism of miR-193b in AD. Inflamed human keratinocytes (HaCaT) were established by tumor necrosis factor (TNF)-α/interferon (IFN)-γ stimulation. Cell viability was measured using MTT assay, while the cell cycle was analyzed using flow cytometry. The cytokine levels were examined by enzyme-linked immunosorbent assay. The interaction between Sp1, miR-193b, and HMGB1 was analyzed using dual luciferase reporter and/or chromatin immunoprecipitation (ChIP) assays. Our results revealed that miR-193b upregulation enhanced the proliferation of TNF-α/IFN-γ-treated keratinocytes and repressed inflammatory injury. miR-193b negatively regulated high mobility group box 1 (HMGB1) expression by directly targeting HMGB1. Furthermore, HMGB1 knockdown promoted keratinocyte proliferation and inhibited inflammatory injury by repressing nuclear factor kappa-B (NF-κB) activation. During AD progression, HMGB1 overexpression abrogated increase of keratinocyte proliferation and repression of inflammatory injury caused by miR-193b overexpression. Moreover, transcription factor Sp1 was identified as the biological partner of the miR-193b promoter in promoting miR-193b expression. Therefore, Sp1 upregulation promotes keratinocyte proliferation and represses inflammatory injury during AD development via promoting miR-193b expression and repressing HMGB1/NF-κB activation.

Study on the roles of ß-catenin in hydrogen peroxide-induced senescence in human skin fibroblasts.

Oxidative stress is one of the most important causes of the cellular senescence process. Previous studies showed that ß-catenin can regulate FoxO3a and this association was enhanced in cells exposed to oxidative stress. It has also been reported that ß-catenin can regulate some senescence-related proteins. We propose that ß-catenin may play a crucial role in senescence of normal human primary skin fibroblasts (NHSFs). Here, we explored the roles and mechanisms of ß-catenin on H(2)O(2)-induced senescence in NHSFs. ß-catenin expression was decreased in NHSFs after H(2)O(2) treatment. Overexpression of ß-catenin in NHSFs led to a marked delay of many senescent phenotypes induced by H(2)O(2). Furthermore, overexpression of ß-catenin in NHSFs can antagonise the alteration of reactive oxygen species accumulation and some senescence-related proteins expression induced by H(2)O(2) treatment. Our data demonstrated that ß-catenin can protect NHSFs from H(2)O(2)-induced premature senescence by alleviating oxidative stress and regulating some senescence-related molecules.