Overexpression and potential roles of NRIP1 in psoriasis.
Overexpression and potential roles of NRIP1 in psoriasis.
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DOI：
10.18632/oncotarget.12371
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发表时间：
2016-11-08
期刊：
影响因子：
--
通讯作者：
Yuan R
中科院分区：
文献类型：
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作者：
Luan C;Chen X;Hu Y;Hao Z;Osland JM;Chen X;Gerber SD;Chen M;Gu H;Yuan R
核受体相互作用蛋白1(NRIP1，又称RIP140)是多种转录因子和核受体的共同调节因子，参与调节乳腺发育和炎症反应等多种生物学和病理过程。本研究旨在探讨NRIP1在银屑病发病机制中的作用。30例活动期银屑病患者和16例健康志愿者参加本研究。QRT-PCR分析发现，与银屑病非皮损和正常对照相比，银屑病皮损中NRIP1和RelA/P65均升高，银屑病患者外周血单个核细胞(PBMC)中NRIP1和RelA/P65也呈高表达。抑制HaCaT细胞中的NRIP1可以显著抑制细胞生长和诱导细胞凋亡，而抑制银屑病患者分离的CD4+T细胞中的NRIP1可以下调RelA/p65的表达，减少IL-17的分泌。此外，在Nrig1基因敲除小鼠中，ImQ诱导的皮肤炎症反应延迟，皮损中relA/p65的表达减少。综上所述，我们的研究结果提示，NRIP1在银屑病患者的皮肤和PBMC中均有过表达，并可能通过调节RelA/p65参与角质形成细胞的异常增殖和凋亡以及免疫反应。因此，NRIP1可能是治疗银屑病的潜在靶点。
Nuclear receptor interacting protein 1 (NRIP1, also known as RIP140) is a co-regulator for various transcriptional factors and nuclear receptors, and has been shown to take part in many biological and pathological processes, such as regulating mammary gland development and inflammatory response. The aim of this study is to investigate the expression of NRIP1 and to explore its roles in the pathogenesis of psoriasis. Thirty active psoriasis patients and 16 healthy volunteers were enrolled for this study. qRT-PCR analyses found that both NRIP1 and RelA/p65 were elevated in psoriatic lesions compared to psoriatic non-lesions and normal controls, and also overexpressed in peripheral blood mononuclear cell (PBMCs) of psoriasis patients. Suppression of NRIP1 in HaCaT cells could significantly inhibit cell growth and induce apoptosis, and the suppression of NRIP1 in CD4+ T cells isolated from psoriasis patients could downregulate the expression of RelA/p65 and decrease the secretion of IL-17. Furthermore, in Nrip1 knockout mice, IMQ-induced inflammation of skin was delayed and the RelA/p65 expression in lesions was reduced. In conclusion, our data suggests that NRIP1 is overexpressed both in skin and PBMCs of psoriasis patients and may be involved in the abnormal proliferation and apoptosis of keratinocytes, as well as the immune reaction through the regulation of RelA/p65. Therefore, NRIP1 may be a potential therapeutic target for psoriasis.