Makino Teruhiko, Mizawa Megumi, Takemoto Keita, Yamamoto Seiji, Shimizu Tadamichi
Department of Dermatology Faculty of Medicine Academic Assembly University of Toyama Toyama Japan.
Department of Pathology Faculty of Medicine Academic Assembly University of Toyama Toyama Japan.
Skin Health Dis. 2024 Sep 5;4(6):e440. doi: 10.1002/ski2.440. eCollection 2024 Dec.
Filaggrin-2 (FLG2) and hornerin (HRNR) are members of the S100 fused-type protein family, which share many properties with filaggrin (FLG). A previous study demonstrated that the expression of FLG2 was significantly decreased in psoriatic skin relative to that in normal skin. In contrast, the HRNR expression in psoriatic skin varied among studies.
We aimed to investigate the effect of tumour necrosis factor-α (TNF-α), IL-17A and IL-22 on the expression of FLG2 and HRNR using a three-dimensional psoriatic skin model.
In the present study, we generated a 3D psoriatic skin model that was stimulated with TNF-α, IL-17A and IL-22 for 3D skin equivalents. Using this model, we examined the altered expression of FLG2 and HRNR by quantitative reverse transcription polymerase chain reaction and immunostaining.
In the 3D psoriatic skin model, the expression of FLG2 and HRNR was significantly reduced compared with that in the 3D control skin. FLG2 expression was significantly decreased by stimulation with TNF-α, IL-17A and IL-22. In contrast, the expression of HRNR was markedly increased by stimulation with IL-22, although it was slightly decreased by TNF-α or IL-17A compared to the 3D control skin.
TNF-α, IL-17A and IL-22 have different effects on FLG2 and HRNR expression and epidermal structure formation. Furthermore, FLG2 and HRNR may play different roles in barrier formation and the pathogenesis of psoriasis.
丝聚合蛋白-2(FLG2)和角蛋白(HRNR)是S100融合型蛋白家族的成员,它们与丝聚合蛋白(FLG)具有许多共同特性。先前的一项研究表明,与正常皮肤相比,银屑病皮肤中FLG2的表达显著降低。相比之下,银屑病皮肤中HRNR的表达在不同研究中有所不同。
我们旨在使用三维银屑病皮肤模型研究肿瘤坏死因子-α(TNF-α)、白细胞介素-17A(IL-17A)和白细胞介素-22(IL-22)对FLG2和HRNR表达的影响。
在本研究中,我们构建了一个三维银屑病皮肤模型,用TNF-α、IL-17A和IL-22刺激该模型以获得三维皮肤等效物。使用该模型,我们通过定量逆转录聚合酶链反应和免疫染色检测了FLG2和HRNR表达的变化。
在三维银屑病皮肤模型中,与三维对照皮肤相比,FLG2和HRNR的表达显著降低。TNF-α、IL-17A和IL-22刺激后,FLG2表达显著降低。相比之下,IL-22刺激后HRNR表达显著增加,尽管与三维对照皮肤相比,TNF-α或IL-17A刺激后HRNR表达略有降低。
TNF-α、IL-17A和IL-22对FLG2和HRNR表达以及表皮结构形成具有不同影响。此外,FLG2和HRNR可能在屏障形成和银屑病发病机制中发挥不同作用。