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环状 EIF5 通过 p-NFκB 和 p-STAT3 信号通路促进银屑病角质形成细胞的过度增殖和炎症。

CircEIF5 contributes to hyperproliferation and inflammation of keratinocytes in psoriasis via p-NFκB and p-STAT3 signalling pathway.

机构信息

Department of Dermatology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

出版信息

Exp Dermatol. 2022 Aug;31(8):1145-1153. doi: 10.1111/exd.14565. Epub 2022 Mar 18.

DOI:10.1111/exd.14565
PMID:35288970
Abstract

Psoriasis is a chronic, immune-mediated skin disease accompanied by hyperproliferation and inflammation of keratinocytes. Circular RNAs (circRNAs) as new players regulating the development of psoriasis have been reported in recent years. However, its mechanism has not yet been fully revealed. In this study, we identified that hsa_circ_0033469 (circEIF5) was highly expressed in psoriasis tissues compared with the normal skin. We investigated the functional roles of circEIF5 in proliferation and inflammatory of HaCat cells under M5-stimulated inflammatory condition. By using a approach of knockdown and overexpression of circEIF5, we showed that circEIF5 could promote proliferation by facilitating the G1/S transition and increase secretion of chemokines in HaCat cells. These moderating effects of circEIF5 were associated with the activating of the NF-κB and STAT3 signalling pathways. Moreover, NF-κB and STAT3 inhibition abrogated circEIF5-induced promotion of cell proliferation and chemokine secretion. These results indicated that through NF-κB and STAT3 signalling pathways, circEIF5 regulated the proliferation and chemokine secretion of HaCat cells and contributed to the pathogenesis of psoriasis, which might become a potent target for psoriasis treatment.

摘要

银屑病是一种慢性、免疫介导的皮肤疾病,伴有角质形成细胞的过度增殖和炎症。近年来,已有研究报道环状 RNA(circRNA)作为调节银屑病发展的新调控因子。然而,其机制尚未完全阐明。在本研究中,我们发现 hsa_circ_0033469(circEIF5)在银屑病组织中的表达明显高于正常皮肤。我们研究了 circEIF5 在 M5 刺激炎症条件下对 HaCat 细胞增殖和炎症的功能作用。通过使用 circEIF5 敲低和过表达的方法,我们发现 circEIF5 可以通过促进 G1/S 期转换促进增殖,并增加 HaCat 细胞中趋化因子的分泌。circEIF5 的这些调节作用与 NF-κB 和 STAT3 信号通路的激活有关。此外,NF-κB 和 STAT3 的抑制消除了 circEIF5 诱导的促进细胞增殖和趋化因子分泌的作用。这些结果表明,circEIF5 通过 NF-κB 和 STAT3 信号通路调节 HaCat 细胞的增殖和趋化因子分泌,促进银屑病的发病机制,可能成为银屑病治疗的有效靶点。

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