CircEIF5 contributes to hyperproliferation and inflammation of keratinocytes in psoriasis via p-NFκB and p-STAT3 signalling pathway
CircEIF5 contributes to hyperproliferation and inflammation of keratinocytes in psoriasis via p-NFκB and p-STAT3 signalling pathway
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DOI：
10.1111/exd.14565
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发表时间：
2022-03-18
影响因子：
3.6
通讯作者：
Sun, Qing
中科院分区：
文献类型：
--
作者：
Chen, Cheng;Yang, Zhenxian;Sun, Qing
银屑病是一种慢性、免疫介导的皮肤病，伴有角质形成细胞过度增殖和炎症。环状RNA（circular RNA，circRNA）作为调控银屑病发生发展的新的参与者，近年来被报道。但其作用机制尚未完全揭示。在这项研究中，我们发现hsa_circ_0033469（circEIF 5）在银屑病组织中的表达高于正常皮肤。我们研究了circEIF 5在M5刺激的炎症条件下HaCat细胞增殖和炎症中的功能作用。通过使用敲低和过表达circEIF 5的方法，我们表明circEIF 5可以通过促进HaCat细胞中的G1/S转换和增加趋化因子的分泌来促进增殖。circEIF 5的这些调节作用与NF-κ B和STAT 3信号通路的激活相关。此外，NF-κ B和STAT 3抑制废除circEIF 5诱导的细胞增殖和趋化因子分泌的促进。这些结果表明，circEIF 5通过NF-κ B和STAT 3信号通路调控HaCat细胞增殖和趋化因子分泌，参与银屑病的发病机制，可能成为银屑病治疗的有效靶点。
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-kappa B and STAT3 signalling pathways. Moreover, NF-kappa B and STAT3 inhibition abrogated circEIF5-induced promotion of cell proliferation and chemokine secretion. These results indicated that through NF-kappa B 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.