Downregulated miR-187 contributes to the keratinocytes hyperproliferation in psoriasis

Downregulated miR-187 contributes to the keratinocytes hyperproliferation in psoriasis
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下调的 miR-187 导致银屑病角质形成细胞过度增殖

DOI:
10.1002/jcp.27135
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发表时间:
2019
影响因子:
5.6
通讯作者:
Zheng Guangjuan
Zheng Guangjuan
中科院分区:
生物学2区
文献类型:
--
作者:
Tang Lipeng;He Songmin;Zhu Ying;Feng Bing;Su Zuqing;Liu Bo;Xu Fangfang;Wang Xieqi;Liu Hongying;Li Chutian;Zhao Jie;Zheng Xirun;Li Caiyun;Sun Chaoyue;Lu Chuanjian;Zheng Guangjuan

文献摘要

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银屑病是一种以表皮增生和炎症为特征的常见慢性皮肤病。然而,银屑病的发病机制是多因素的,并没有完全理解。microRNA(miRNAs)是一类很有前途的非编码小RNA分子,通过调控基因表达对细胞功能有很大影响。在这里,我们报告了microRNA-187(miR-187),这是在深度筛选miRNAs谱中鉴定的最具活力的microRNA之一,在炎症细胞因子刺激的角质形成细胞和银屑病皮肤中下调。通过荧光素酶活性测定和功能获得研究,我们发现miR-187通过靶向CD 276抑制角质形成细胞过度增殖。此外,miR-187的过表达减少了银屑病小鼠模型中的棘皮症并降低了疾病的严重程度。综上所述,我们的研究结果表明miR-187是银屑病发病机制中的关键因素,可能是银屑病治疗的有效靶点。
Psoriasis is a common chronic skin disease characterized by epidermal hyperplasia and inflammation. However, the pathogenesis of psoriasis is multifactorial and is not fully understood. MicroRNAs (miRNAs) represent a promising class of small, noncoding RNA molecules that have a large impact on cellular functions by regulating gene expression. Here we reported that microRNA‐187 (miR‐187), which is one of the most dynamic microRNAs identified in the deep screening miRNAs profile, is downregulated in inflammatory cytokines‐stimulated keratinocytes and psoriatic skins. By luciferase activity assay and gain‐of‐function studies, we showed that miR‐187 inhibits keratinocytes hyperproliferation by targeting CD276. Moreover, overexpression of miR‐187 decreases acanthosis and reduces the disease severity in psoriasis mouse models. Taken together, the results of our study implies miR‐187 as a critical factor in psoriasis pathogenesis, which could be a potent target for psoriasis treatment.