Periostin Expression Is Elevated in HDM-Driven Allergic Airway Disease and Associated with Increased Pericyte Migration
Periostin Expression Is Elevated in HDM-Driven Allergic Airway Disease and Associated with Increased Pericyte Migration
复制标题
HDM 驱动的过敏性气道疾病中 Periostin 表达升高，并与周细胞迁移增加相关
DOI：
10.1164/ajrccm-conference.2021.203.1_meetingabstracts.a4495
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Johnson J
中科院分区：
文献类型：
--
作者：
Johnson J
周细胞是一种组织常驻间充质干细胞，已被证明有助于组织重塑和纤维化。在过敏性哮喘中，周细胞通过解偶联并从血管向气道壁迁移来实现这一目标，在那里它们有助于平滑肌增厚并分化为形成疤痕的肌成纤维细胞。控制纤维化中细胞迁移的信号在很大程度上是未知的，但被认为包括生长因子和细胞因子的混合物，如TGF-β、EGF和骨膜蛋白。关于该系统中骨膜素的来源，以及其对细胞迁移的影响和与其他生长因子TGF-β的相互作用，一直存在争议。假设在纤维化过程中周细胞产生骨膜蛋白，并与TGF-β相互作用以促进周细胞迁移。一系列体外和离体方法被用来询问这一点，包括蛋白质表达和迁移测定。方法体外培养人周细胞，用抗骨膜蛋白抗体染色。使用共聚焦显微镜对周细胞进行成像以评估骨膜蛋白的定位和表达。Transwell和划痕实验采用TGF-β或骨膜蛋白预处理的人周细胞进行。对暴露于屋尘螨（HDM）引起的变应性气道疾病小鼠的肺切片也进行了骨膜蛋白染色，以探索其在纤维化肺部疾病中的作用。elisa法检测支气管肺泡灌洗液中骨膜蛋白的表达水平。结果免疫组化染色显示周细胞强烈表达骨膜蛋白，TGF-β处理后表达增加。迁移实验表明，与TGF-β处理的细胞相似，用骨膜素处理的细胞更具迁移性。HDM暴露小鼠的Periostin表达也增加。结论经TGF-β刺激的周细胞可产生骨膜蛋白，骨膜蛋白在诱导周细胞迁移中起关键作用。TGF-β处理周细胞中骨膜蛋白表达的增加表明TGF-β调节骨膜蛋白表达，促进组织纤维化背景下周细胞迁移，尽管需要进一步的实验来阐明这种相互作用的机制。
RATIONALEPericytes are a type of tissue-resident mesenchymal stem cell that have been shown to contribute to tissue remodelling and fibrosis. In allergic asthma, pericytes achieve this by uncoupling and migrating away from blood vessels toward the airway wall, where they contribute to smooth muscle thickening and differentiate into scar-forming myofibroblasts. The signals that control cell migration in fibrosis are largely unknown, but are thought to include a cocktail of growth factors and cytokines such as TGF-β, EGF, and periostin. There is an ongoing debate about the source of periostin within this system, as well as its effect on cell migration and interactions with other growth factors, namely TGF-β. It is hypothesised that periostin is produced by pericytes during fibrosis and interacts with TGF-β in order to facilitate pericyte migration. A range of in vitro and ex vivo methods were utilised to interrogate this, including protein expression and migration assays.METHODSHuman pericytes were cultured in vitro and stained using an anti-periostin antibody. Pericytes were imaged using confocal microscopy to assess the localisation and expression of periostin. Transwell and scratch assays were performed using human pericytes that had been pretreated with TGF-β or periostin. Lung sections from mice with allergic airway disease driven by exposure to house dust mite (HDM) were also stained for periostin to explore its involvement in fibrotic lung disease. ELISAs were also carried out to asses periostin expression levels in bronchoalveolar lavage fluid.RESULTSImmunostaining indicated that pericytes robustly express periostin, with increased expression following treatment with TGF-β. Migration assays demonstrated that cells treated with periostin were more migratory, similar to those treated with TGF-β. Periostin expression was also increased in HDM exposed mice.CONCLUSIONSPeriostin is produced by pericytes stimulated with TGF-β, and periostin plays a key role in inducing pericyte migration. The increase in periostin expression in TGF-β treated pericytes suggests that TGF-β modulates periostin expression to promote pericyte migration in the context of tissue fibrosis, although further experimentation should be performed to elucidate the mechanism of this interaction.