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下调的 miR-187 导致银屑病角质形成细胞过度增殖。

Downregulated miR-187 contributes to the keratinocytes hyperproliferation in psoriasis.

机构信息

Deparment of Pharmacology of Traditional Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

The Postdoctoral Research Station, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.

出版信息

J Cell Physiol. 2019 Apr;234(4):3661-3674. doi: 10.1002/jcp.27135. Epub 2018 Sep 14.

DOI:10.1002/jcp.27135
PMID:30607907
Abstract

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.

摘要

银屑病是一种常见的慢性皮肤病,其特征是表皮过度增生和炎症。然而,银屑病的发病机制是多因素的,尚未完全阐明。microRNAs(miRNAs)是一类具有很大影响力的小非编码 RNA 分子,通过调节基因表达来影响细胞功能。在这里,我们报告说,在炎症细胞因子刺激的角质细胞和银屑病皮肤中,miR-187(miR-187)这种在深度筛选 miRNAs 谱中鉴定出的最具活力的 microRNAs 之一,其表达下调。通过荧光素酶活性测定和功能获得研究,我们表明 miR-187 通过靶向 CD276 抑制角质细胞过度增殖。此外,miR-187 的过表达可减少银屑病小鼠模型中的棘层肥厚并降低疾病严重程度。总之,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。

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