ILF2 Contributes to Hyperproliferation of Keratinocytes and Skin Inflammation in a KLHDC7B-DT-Dependent Manner in Psoriasis.
ILF2 Contributes to Hyperproliferation of Keratinocytes and Skin Inflammation in a KLHDC7B-DT-Dependent Manner in Psoriasis.
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DOI：
10.3389/fgene.2022.890624
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发表时间：
2022
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
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背景：白细胞介素2增强因子2(ILF2)广泛参与RNA的稳定性和炎症反应。长非编码RNA(LncRNA)的异常表达与银屑病的发病机制有关。然而，对ILF2在银屑病中的作用知之甚少。目的：探讨白介素2和KLHDC7B-DT在银屑病发病中的作用。方法：采用LncRNA芯片和定量逆转录聚合酶链式反应技术检测银屑病组织中LncRNA的表达。用正常人表皮角质形成细胞、HaCaT细胞和M5刺激的Ker-CT细胞(IL-17A、IL-22、IL-1α、抑瘤素M和肿瘤坏死因子-α)建立体外银屑病模型。用荧光原位杂交法检测KLHDC7B-DT和ILF2在角质形成细胞中的分布。采用EDU比色法和流式细胞仪检测KLHDC7B-DT和ILF2对角质形成细胞的增殖作用。采用酶联免疫吸附试验检测细胞因子的分泌水平。用RNA下拉和RNA免疫沉淀(RIP)检测KLHDC7B-DT与ILF2的直接结合。Western blotting检测STAT3/JNK信号通路相关蛋白。结果：ILF2和KLHDC7B-DT在银屑病组织和M5诱导的角质形成细胞中高表达。KLHDC7B-DT促进角质形成细胞增殖，并诱导IL-6和IL-8的分泌。KLHDC7B-DT可直接与ILF2结合，激活STAT3和JNK信号通路。KLHDC7B-DT的表达受ILF2的调控。ILF2基因敲除后，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，我们还发现ILF2以KLHDC7B-DT依赖的方式促进角质形成细胞的增殖和炎症反应。结论：ILF2和KLHDC7B-DT参与了银屑病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。
Background: 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. Objective: To investigate the role of ILF2 and KLHDC7B-DT in psoriasis. Methods: 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 in vitro. Fluorescence in situ 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. Results: 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. Conclusions: 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.
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DOI：
10.4049/jimmunol.1100123
发表时间：
2011-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lin AM;Rubin CJ;Khandpur R;Wang JY;Riblett M;Yalavarthi S;Villanueva EC;Shah P;Kaplan MJ;Bruce AT
通讯作者：
Bruce AT
IL-22 诱导的 miR-122-5p 通过靶向 Sprouty2 促进角质形成细胞增殖
影响因子：
3.6
作者：
Jiang, Meng;Ma, Weiyuan;Sun, Qing
通讯作者：
Sun, Qing
影响因子：
11.8
作者：
Jia, Yangyang;Li, Xin;Jiang, Yiguo
通讯作者：
Jiang, Yiguo
影响因子：
6
作者：
Li, Mu-xing;Wang, Hang-yan;Xiu, Dian-rong
通讯作者：
Xiu, Dian-rong
影响因子：
5.3
作者：
Kuwano, Yuki;Kim, Hyeon Ho;Gorospe, Myriam
通讯作者：
Gorospe, Myriam