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角质形成细胞和表皮转谷氨酰胺酶的激活及上调与银屑病皮损中其底物的消耗有关。

Activation and upregulation of keratinocyte and epidermal transglutaminases are associated with depletion of their substrates in psoriatic lesions.

作者信息

Alharbi N S, Almami I S

机构信息

Department of Biology, College of Science, Qassim University, Buraydah, Al-Qassim, Saudi Arabia.

出版信息

Eur Rev Med Pharmacol Sci. 2023 Dec;27(23):11281-11293. doi: 10.26355/eurrev_202312_34567.

DOI:10.26355/eurrev_202312_34567
PMID:38095377
Abstract

OBJECTIVE

Psoriasis is a chronic skin disorder caused by abnormal interactions between epidermal and immune cells. Thus, the interplay between the proliferation and differentiation of epidermal components should be tightly regulated to protect against psoriasis. The differentiation process is primarily controlled by transglutaminases (TGs). However, studies on TG enzymes and their molecular alterations in psoriatic skin lesions are limited. Therefore, this study aimed to investigate TG activity and gene and protein expression in human psoriatic and normal skin tissues.

MATERIALS AND METHODS

Keratinocyte TG (TG1), and epidermal TG (TG3) activity, localization, protein levels, and gene expression in human psoriatic skin were determined by immunohistochemistry and RT-qPCR. The expression of TG substrates (loricin and involucrin - IVL) was also investigated using RT-qPCR.

RESULTS

TG1 and TG3 enzymatic activities and gene expression were significantly higher in psoriatic skin tissue than in normal skin tissue. However, both TGs were present in the same location and were equally highly expressed. Moreover, the expression of two TG substrates (loricin and involucrin) was significantly decreased compared to that in psoriatic and healthy skin samples.

CONCLUSIONS

The activation and upregulation of TG1 and TG3 result from the depletion of their substrates (loricin and involucrin), both of which play a major role in the pathogenicity of psoriatic skin tissue and are necessary for proper skin development.

摘要

目的

银屑病是一种由表皮细胞与免疫细胞之间异常相互作用引起的慢性皮肤疾病。因此,表皮成分的增殖与分化之间的相互作用应受到严格调控以预防银屑病。分化过程主要由转谷氨酰胺酶(TGs)控制。然而,关于TG酶及其在银屑病皮肤病变中的分子改变的研究有限。因此,本研究旨在调查人银屑病皮肤组织和正常皮肤组织中的TG活性、基因及蛋白表达。

材料与方法

采用免疫组织化学和RT-qPCR法测定人银屑病皮肤中的角质形成细胞TG(TG1)和表皮TG(TG3)的活性、定位、蛋白水平及基因表达。还使用RT-qPCR法研究了TG底物(loricin和内披蛋白-IVL)的表达。

结果

银屑病皮肤组织中TG1和TG3的酶活性及基因表达显著高于正常皮肤组织。然而,两种TG位于相同位置且表达水平相当。此外,与银屑病和健康皮肤样本相比,两种TG底物(loricin和内披蛋白)的表达显著降低。

结论

TG1和TG3的激活及上调是由于其底物(loricin和内披蛋白)的消耗所致,这两者在银屑病皮肤组织的致病性中起主要作用,且对正常皮肤发育是必需的。

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