Aquaporin-3 (AQP3), a water/glycerol-transporting protein that facilitates water, urea, and glycerol transport, can inhibit arsenite-induced apoptosis by up-regulating Bcl-2. However, whether it has a protective role in ultraviolet A (UVA)-induced apoptosis in normal human skin fibroblasts is not known. In this study, we demonstrate that mild UVA treatment fails to induce oxidative cell stress and apoptosis in normal human skin fibroblasts (NHSFs) overexpressing AQP3. After severe UVA irradiation, there was an increase in oxidative cell stress and apoptosis when AQP3 levels decreased. We also found that silencing AQP3 sensitized NHSFs to low-dose UVA. Overexpressing AQP3 was protective against high-dose UVA-induced oxidative stress and apoptosis. Besides, we observed that Bcl-2 may be involved in UVA-induced apoptosis. Our findings suggested that the water/glycerol-transporting protein AQP3 plays a role in resistance to UVA-induced apoptosis.

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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.