微小 RNA-125a 与银屑病严重程度和炎症降低相关，并抑制角质形成细胞增殖。

MicroRNA-125a Correlates with Decreased Psoriasis Severity and Inflammation and Represses Keratinocyte Proliferation.

机构信息

Department of Dermatology, The First Hospital of China Medical University, Shenyang, China.

Department of Dermatology, The Seventh People's Hospital of Shenyang, Shenyang, China.

出版信息

Dermatology. 2021;237(4):568-578. doi: 10.1159/000510681. Epub 2021 Mar 18.

DOI:10.1159/000510681

PMID:33735868

Abstract

BACKGROUND

Psoriasis has a complex etiology related to inflammation and dysregulated immune system. MicroRNA (miR)-125a is a miRNA intimately related to inflammation and immunity; therefore, we presumed that it might play a role in the pathogenesis of psoriasis. This study aimed to investigate the correlation of miR-125a with disease severity and inflammation in psoriasis patients, and the effect of miR-125a on proliferation, apoptosis as well as its target signaling pathway in keratinocytes.

METHODS

Sixty psoriasis patients were consecutively recruited, then lesional and non-lesional skin tissue samples were collected. miR-125a in lesional and non-lesional skin tissues, tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and IL-17 mRNA expressions in lesional skin tissues were detected. Then, miR-125a overexpression, control overexpression, miR-125a knockdown and control knockdown plasmids were transfected into HaCaT cells. Subsequently, cell proliferation, apoptosis, IL-23R, JAK2, and STAT3 expressions were assessed.

RESULTS

miR-125a was reduced in lesional skin tissue compared with non-lesional skin tissue (p < 0.001), and it distinguished lesional skin tissue from non-lesional skin tissue with a high area under curve of 0.917 (95% CI 0.866-0.968). Negative association of miR-125a in lesional skin tissue with lesional body surface area (p = 0.037) and psoriasis area and severity index score (p < 0.001) was found. Additionally, miR-125a was negatively correlated with TNF-α (p = 0.001), IL-1β (p = 0.014), and IL-17 (p = 0.003) in lesional skin tissue. In cellular experiments, miR-125a overexpression inhibited proliferation and promoted apoptosis, while miR-125a knockdown enhanced proliferation and repressed apoptosis in HaCaT cells. Additionally, miR-125a negatively regulated the IL-23R/JAK2/STAT3 pathway in HaCaT cells.

CONCLUSION

miR-125a could facilitate the disease monitoring and probably has the potential to be a therapeutic target in psoriasis.

摘要

背景

银屑病的发病机制与炎症和免疫系统失调有关。微小 RNA（miR）-125a 与炎症和免疫密切相关；因此，我们推测它可能在银屑病的发病机制中发挥作用。本研究旨在探讨 miR-125a 与银屑病患者疾病严重程度和炎症的相关性，以及 miR-125a 对角质形成细胞增殖、凋亡及其靶信号通路的影响。

方法

连续招募 60 例银屑病患者，采集皮损和非皮损皮肤组织标本。检测皮损和非皮损皮肤组织中的 miR-125a 及皮损皮肤组织中肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6 和 IL-17 mRNA 表达。然后，将 miR-125a 过表达、对照过表达、miR-125a 敲低和对照敲低质粒转染入 HaCaT 细胞。随后，评估细胞增殖、凋亡、IL-23R、JAK2 和 STAT3 表达。

结果

与非皮损皮肤组织相比，皮损皮肤组织中 miR-125a 降低（p＜0.001），且 miR-125a 区分皮损皮肤组织与非皮损皮肤组织的曲线下面积为 0.917（95%CI 0.866-0.968）。miR-125a 在皮损皮肤组织中的表达与皮损体表面积（p=0.037）和银屑病面积和严重程度指数评分（p＜0.001）呈负相关。此外，miR-125a 与皮损皮肤组织中 TNF-α（p=0.001）、IL-1β（p=0.014）和 IL-17（p=0.003）呈负相关。在细胞实验中，miR-125a 过表达抑制增殖并促进凋亡，而 miR-125a 敲低则增强增殖并抑制凋亡。此外，miR-125a 负调控 HaCaT 细胞中的 IL-23R/JAK2/STAT3 通路。