rhIL23R-CHR/Fc融合蛋白通过下调ENST00000522718抑制Act-HaCaT细胞炎症和增殖

rhIL23R-CHR/Fc fusion protein inhibits Act-HaCaT inflammation and proliferation by downregulating ENST00000522718

银屑病是一种以慢性皮肤炎症为主要特征的自身免疫性疾病,其病因及发病机制尚未完全阐明。本研究在前期rhIL23R-CHR/Fc融合蛋白显著改善银屑病小鼠症状并初步阐明药理机制的基础上,利用TNF-α刺激人皮肤永生化角质形成细胞株(HaCat),建立银屑病细胞模型(Act-HaCaT),通过转录组测序并结合qRT-PCR,筛选rhIL23R-CHR/Fc融合蛋白调控Act-HaCaT细胞功能时发挥关键作用的lncRNA分子。研究结果表明,rhIL23R-CHR/Fc融合蛋白能够显著抑制Act-HaCaT细胞增殖和炎症因子产生,通过筛选得到lncRNA ENST00000522718,并发现敲低ENST00000522718能够显著抑制细胞增殖和炎症因子产生,提示ENST00000522718在银屑病的病理机制中发挥着重要作用。

Psoriasis is an autoimmune disease characterized by chronic skin inflammation,and its etiology and pathogenesis have not been fully elucidated to date.In the previous study,rhIL23R-CHR/Fc fusion protein had been found to significantly relieve the symptoms of psoriasis mice and the pharmacological mechanism had been initially elucidated.In this study,we established a psoriasis cell model(Act-HaCaT)using TNF-α-activated human immortalized keratinocytes(HaCat).In our current study,the lncRNA that plays a key role in the regulation of Act-HaCaT function by the rhIL23R-CHR/Fc fusion protein was screened by transcriptome sequencing combined with qRT-PCR.The results showed that rhIL23R-CHR/Fc fusion protein significantly inhibited cell proliferation and inflammatory factor production in Act-HaCaT.lncRNA ENST00000522718 was obtained by screening,and knockdown of ENST00000522718 was found to significantly inhibit cell proliferation and inflammatory factor production.Our findings suggest that ENST00000522718 plays an important role in the pathological mechanism of psoriasis.