Yin Xiran, Yang Zhenxian, Zhu Mingsheng, Chen Cheng, Huang Shan, Li Xueqing, Zhong Hua, Wen He, Sun Qing, Yu Xiaojing, Yan Jianjun
Department of Dermatology, Qilu Hospital, Shandong University, Jinan, China.
Laboratory of Basic Medical Science, Qilu Hospital, Shandong University, Jinan, China.
Front Genet. 2022 May 2;13:890624. doi: 10.3389/fgene.2022.890624. eCollection 2022.
The extensive involvement of interleukin enhancer binding factor 2 (ILF2) in RNA stability and the inflammatory response is well documented. Aberrant long noncoding RNA (lncRNA) expression contributes to the pathogenesis of psoriasis. However, little is known about the role of ILF2 in psoriasis. To investigate the role of ILF2 and KLHDC7B-DT in psoriasis. LncRNA expression in psoriatic tissues was measured by lncRNA microarray and qRT-PCR. Normal human epidermal keratinocytes (NHEKs), HaCaT cells, and Ker-CT cells stimulated with M5 (IL-17A, IL-22, IL-1α, oncostatin M, and TNF-α) were used to establish a psoriasis model . Fluorescence hybridization was used to detect the distribution of KLHDC7B-DT and ILF2 in keratinocytes. The proliferative effects of KLHDC7B-DT and ILF2 on keratinocytes were demonstrated by EdU assay and flow cytometry. ELISA was used to detect the secretion levels of cytokines. RNA pull-down and RNA immunoprecipitation (RIP) were used to detect the direct binding of KLHDC7B-DT with ILF2. Western blotting was used to detect the proteins related to STAT3/JNK signalling pathways. ILF2 and KLHDC7B-DT were significantly overexpressed in psoriatic tissues and M5-induced keratinocytes. KLHDC7B-DT promoted the proliferation of keratinocytes and induced the secretion of IL-6 and IL-8. KLHDC7B-DT could directly bind to ILF2 and activate the STAT3 and JNK signalling pathways. KLHDC7B-DT expression was regulated by ILF2. M5-induced proliferation and inflammatory cytokine secretion in keratinocytes was inhibited after ILF2 knockdown. Furthermore, we found that ILF2 promoted keratinocyte proliferation and the inflammatory response in a KLHDC7B-DT-dependent manner. ILF2 and KLHDC7B-DT are involved in the hyperproliferation of keratinocytes and skin inflammation in psoriasis. In addition, ILF2 functions in a KLHDC7B-DT-dependent manner.
白细胞介素增强子结合因子2（ILF2）在RNA稳定性和炎症反应中的广泛参与已有充分记录。异常的长链非编码RNA（lncRNA）表达促成了银屑病的发病机制。然而，关于ILF2在银屑病中的作用知之甚少。为了研究ILF2和KLHDC7B-DT在银屑病中的作用。通过lncRNA微阵列和qRT-PCR检测银屑病组织中的lncRNA表达。用M5（白细胞介素-17A、白细胞介素-22、白细胞介素-1α、制瘤素M和肿瘤坏死因子-α）刺激的正常人表皮角质形成细胞（NHEK）、HaCaT细胞和Ker-CT细胞用于建立银屑病模型。荧光杂交用于检测KLHDC7B-DT和ILF2在角质形成细胞中的分布。EdU检测和流式细胞术证实了KLHDC7B-DT和ILF2对角质形成细胞的增殖作用。ELISA用于检测细胞因子的分泌水平。RNA下拉和RNA免疫沉淀（RIP）用于检测KLHDC7B-DT与ILF2的直接结合。蛋白质印迹法用于检测与STAT3/JNK信号通路相关的蛋白质。ILF2和KLHDC7B-DT在银屑病组织和M5诱导的角质形成细胞中显著过表达。KLHDC7B-DT促进角质形成细胞的增殖并诱导白细胞介素-6和白细胞介素-8的分泌。KLHDC7B-DT可直接与ILF2结合并激活STAT3和JNK信号通路。KLHDC7B-DT的表达受ILF2调控。ILF2敲低后，M5诱导的角质形成细胞增殖和炎性细胞因子分泌受到抑制。此外，我们发现ILF2以KLHDC7B-DT依赖的方式促进角质形成细胞增殖和炎症反应。ILF2和KLHDC7B-DT参与银屑病中角质形成细胞的过度增殖和皮肤炎症。此外，ILF2以KLHDC7B-DT依赖的方式发挥作用。
