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骨膜蛋白参与犬特应性皮炎病理生理学的研究

A study on periostin involvement in the pathophysiology of canine atopic skin.

作者信息

Mineshige Takayuki, Kamiie Junichi, Sugahara Go, Shirota Kinji

机构信息

Laboratory of Veterinary Pathology, School of Veterinary Medicine, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, Japan.

Present address: Marmoset Research Department, Central Institute for Experimental Animals, 3-25-12 Tonomachi, Kawasaki-ku, Kawasaki, Kanagawa 210-0821, Japan.

出版信息

J Vet Med Sci. 2018 Jan 27;80(1):103-111. doi: 10.1292/jvms.17-0453. Epub 2017 Nov 27.

Abstract

Atopic dermatitis (AD) is a chronic, pruritic, and allergic skin disease in humans and animals, particularly dogs. Canine AD (cAD) has received attention as a spontaneous atopic animal model because domesticated dogs inhabit a human environment, and cAD shares several clinicopathological features with human AD (hAD). In hAD, periostin (PO) is suggested to play a critical role in the enhancement and chronicity of allergic skin inflammation; however, PO involvement in the pathogenesis of cAD is unknown. Here we aimed to clarify PO involvement in the pathophysiology of cAD and focused on the inducing factor and function of PO in canine atopic skin. Using double-labeled in situ hybridization (ISH), interleukin (IL)-13 mRNA-positive cells were detected near the keratinocytes and dermal fibroblasts expressing PO mRNA in atopic skin. Using an in vitro assay, IL-13 induced PO gene expression in both canine dermal fibroblasts and keratinocytes. PO enhanced in vitro growth of canine keratinocytes. Moreover, among PO-induced genes in cultured canine keratinocytes detected using a microarray, we identified IL-25 as a possible mediator in canine atopic skin. In addition, real time polymerase chain reaction (PCR) analysis revealed upregulation of IL-25 gene expression in PO-stimulated keratinocytes. These data suggest that IL-13 possibly derived from T helper 2 (Th2) cells stimulates PO production in both keratinocytes and fibroblasts, and then PO may play a critical role in the pathophysiology of cAD, particularly in the enhancement and chronicity of skin lesions via IL-25.

摘要

特应性皮炎(AD)是人和动物,尤其是犬类的一种慢性、瘙痒性过敏性皮肤病。犬特应性皮炎(cAD)作为一种自发性特应性动物模型受到关注,因为家养犬生活在人类环境中,且cAD与人类特应性皮炎(hAD)具有一些临床病理特征。在hAD中,骨膜蛋白(PO)被认为在过敏性皮肤炎症的加重和慢性化过程中起关键作用;然而,PO在cAD发病机制中的作用尚不清楚。在此,我们旨在阐明PO在cAD病理生理学中的作用,并聚焦于PO在犬特应性皮肤中的诱导因子和功能。使用双标记原位杂交(ISH)技术,在特应性皮肤中,在表达PO mRNA的角质形成细胞和真皮成纤维细胞附近检测到白细胞介素(IL)-13 mRNA阳性细胞。通过体外试验,IL-13可诱导犬真皮成纤维细胞和角质形成细胞中PO基因表达。PO可促进犬角质形成细胞的体外生长。此外,在使用微阵列检测的培养犬角质形成细胞中PO诱导的基因中,我们确定IL-25可能是犬特应性皮肤中的一种介质。此外,实时聚合酶链反应(PCR)分析显示,在PO刺激的角质形成细胞中IL-25基因表达上调。这些数据表明,可能来源于辅助性T细胞2(Th2)的IL-13刺激角质形成细胞和成纤维细胞产生PO,然后PO可能在cAD的病理生理学中起关键作用,特别是通过IL-25在皮肤病变的加重和慢性化过程中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a54/5797867/bfe28b8f095d/jvms-80-103-g001.jpg

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