Psoriasis is an immune-mediated chronic inflammatory skin disease. Keratinocyte hyperproliferation has been regarded as a significant event in psoriasis pathogenesis. Considering the vital role of miRNA-mediated mRNA repression in psoriasis pathogenesis, in the present study, we attempted to investigate the mechanism of keratinocyte overproliferation from the point of miRNA-mRNA regulation. Both online microarray expression profiles and experimental results indicated that the expression of LXR-α and PPAR-γ was downregulated in psoriasis lesion skin. LXR-α or PPAR-γ overexpression alone was sufficient to inhibit keratinocyte proliferation, decrease KRT5 and KRT14 protein levels and increase KRT1 and KRT10 protein levels. miR-203 negatively regulated LXR-α and PPAR-γ expression through direct targeting. miR-203 inhibition exerted the opposite effects to LXR-α or PPAR-γ overexpression on HaCaT cells. More importantly, LXR-α or PPAR-γ overexpression could markedly remarkably attenuate the effects of miR-203 overexpression in keratinocytes, indicating that miR-203 promotes keratinocyte proliferation by targeting LXR-α and PPAR-γ. In conclusion, the miR-203-LXR-α/PPAR-γ axis modulates the proliferation of keratinocytes and might be a novel target for psoriasis treatment, which needs further in vivo investigation.

银屑病是一种免疫介导的慢性炎症性皮肤病。角质形成细胞过度增殖被认为是银屑病发病机制中的一个重要事件。考虑到 miRNA 介导的 mRNA 抑制在银屑病发病机制中的重要作用，在本研究中，我们试图从 miRNA-mRNA 调控的角度研究角质形成细胞过度增殖的机制。在线微阵列表达谱和实验结果均表明 LXR-α 和 PPAR-γ 的表达在银屑病病变皮肤中下调。单独的 LXR-α 或 PPAR-γ 过表达足以抑制角质形成细胞增殖，降低 KRT5 和 KRT14 蛋白水平并增加 KRT1 和 KRT10 蛋白水平。miR-203 通过直接靶向负向调节 LXR-α 和 PPAR-γ 的表达。miR-203 抑制对 HaCaT 细胞产生与 LXR-α 或 PPAR-γ 过表达相反的影响。更重要的是，LXR-α 或 PPAR-γ 过表达可以显着减弱 miR-203 过表达对角质形成细胞的影响，表明 miR-203 通过靶向 LXR-α 和 PPAR-γ 促进角质形成细胞增殖。总之，miR-203-LXR-α/PPAR-γ轴调节角质形成细胞的增殖，可能是银屑病治疗的新靶点，需要进一步的体内研究。