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DRP1 表达与银屑病疾病严重程度相关,并调节角质形成细胞功能。

Dynamin-related protein 1 expression correlates with psoriasis disease severity and regulates keratinocyte function.

机构信息

Phase I Clinical Trials Unit, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.

Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, 210008, China.

出版信息

Eur J Dermatol. 2020 Aug 1;30(4):329-337. doi: 10.1684/ejd.2020.3849.

Abstract

BACKGROUND

The pathogenesis of psoriasis is still not fully understood. Dynamin-related protein 1 (Drp1) regulates mitochondrial fission and is implicated in various inflammatory conditions, but research regarding Drp1 in the skin is scarce.

OBJECTIVES

To examine Drp1 expression in psoriasis vulgaris lesional skin and the effect of Drp1 expression on keratinocyte proliferation and inflammatory mediator release in vitro.

MATERIALS AND METHODS

Skin biopsies were collected, and the expression of Drp1 and TNF-α was investigated in the skin. Serum TNF-α level was also examined. The effect of Drp1 on keratinocyte proliferation and inflammatory mediator release was evaluated in HaCaT cells following Drp1 transfection. The effect of TNF-α on Drp1 expression was also studied in HaCaT cells.

RESULTS

Drp1 expression was significantly increased and positively correlated with PASI score and TNF-α expression in skin. In HaCaT cells, Drp1 transfection altered cellular ATP and proliferation, induced G2/M arrest, and affected inflammatory mediator (TNF-α, IL-6 and CXCL8) release. Moreover, TNF-α induced Drp1 expression and recovered cellular ATP content and mediator release.

CONCLUSION

Drp1 is significantly elevated in psoriasis vulgaris skin and positively correlates with disease severity, moreover, in vitro, Drp1 regulates keratinocyte function.

摘要

背景

银屑病的发病机制尚未完全阐明。与动力相关蛋白 1(Drp1)调节线粒体分裂,与各种炎症状态有关,但皮肤中关于 Drp1 的研究较少。

目的

研究寻常型银屑病皮损皮肤中 Drp1 的表达,以及 Drp1 表达对体外角质形成细胞增殖和炎症介质释放的影响。

材料和方法

收集皮肤活检标本,检测皮肤中 Drp1 和 TNF-α 的表达,并检测血清 TNF-α 水平。转染 Drp1 后,在 HaCaT 细胞中评估 Drp1 对角质形成细胞增殖和炎症介质释放的影响。还研究了 TNF-α 对 HaCaT 细胞中 Drp1 表达的影响。

结果

Drp1 表达在皮肤中显著增加,并与 PASI 评分和 TNF-α 表达呈正相关。在 HaCaT 细胞中,Drp1 转染改变了细胞内 ATP 和增殖,诱导 G2/M 期阻滞,并影响炎症介质(TNF-α、IL-6 和 CXCL8)释放。此外,TNF-α 诱导 Drp1 表达并恢复细胞内 ATP 含量和介质释放。

结论

Drp1 在寻常型银屑病皮肤中显著升高,并与疾病严重程度呈正相关,此外,体外 Drp1 调节角质形成细胞功能。

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