Matricellular Protein Periostin Promotes Pericyte Migration in Fibrotic Airways.

Matricellular Protein Periostin Promotes Pericyte Migration in Fibrotic Airways.
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DOI:
10.3389/falgy.2021.786034
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发表时间:
2021
影响因子:
--
通讯作者:
Johnson JR
Johnson JR
中科院分区:
其他
文献类型:
--
作者:
Bignold RE;Johnson JR

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介绍:骨膜蛋白是一种基质细胞蛋白,目前被用作哮喘的生物标志物。然而,其在过敏性哮喘组织重塑中的作用目前尚不清楚。我们以前已经证明,组织驻留间充质干细胞称为周细胞是参与气道重塑的关键细胞类型。这被认为是由周细胞从支持大气道的微血管系统解偶联引起的,由炎性生长因子和细胞因子促进。据推测,骨膜蛋白可能是由促纤维化周细胞产生的,并有助于在过敏性哮喘中观察到的重塑。研究方法:使用抗骨膜蛋白抗体对来自患有由暴露于屋尘螨(HDM)驱动的过敏性气道疾病的小鼠的肺切片进行染色,以探索其在纤维化肺病中的参与。在体外培养人周细胞并对骨膜蛋白染色以评估骨膜蛋白表达。使用用TGF-β或骨膜蛋白预处理的人周细胞进行迁移测定。还进行ELISA以评估支气管肺泡灌洗液中的骨膜蛋白表达水平以及IL-13对骨膜蛋白产生的诱导。结果:免疫组化显示周细胞强烈表达骨膜蛋白,TGF-β处理后表达增加。迁移试验表明,骨膜蛋白处理的周细胞更具迁移性。在HDM暴露的小鼠中以及在用IL-13处理的培养的周细胞中,骨膜蛋白产生也增加。结论:骨膜蛋白是周细胞在TGF-β或IL-13刺激下产生的,在诱导周细胞迁移中起重要作用。TGF-β或IL-13处理的周细胞中骨膜蛋白表达的增加表明IL-13可以触发周细胞中骨膜蛋白的产生,而TGF-β调节骨膜蛋白表达以促进组织纤维化背景下的周细胞迁移。
Introduction: Periostin is a matricellular protein that is currently used as a biomarker for asthma. However, its contribution to tissue remodeling in allergic asthma is currently unknown. We have previously demonstrated that tissue-resident mesenchymal stem cells known as pericytes are a key cell type involved in airway remodeling. This is thought to be caused the uncoupling of pericytes from the microvasculature supporting the large airways, facilitated by inflammatory growth factors and cytokines. It is hypothesized that periostin may be produced by profibrotic pericytes and contribute to the remodeling observed in allergic asthma. Methods: Lung sections from mice with allergic airway disease driven by exposure to house dust mite (HDM) were stained using an anti-periostin antibody to explore its involvement in fibrotic lung disease. Human pericytes were cultured in vitro and stained for periostin to assess periostin expression. Migration assays were performed using human pericytes that were pretreated with TGF-β or periostin. ELISAs were also carried out to assess periostin expression levels in bronchoalveolar lavage fluid as well as the induction of periostin production by IL-13. Results: Immunostaining indicated that pericytes robustly express periostin, with increased expression following treatment with TGF-β. Migration assays demonstrated that pericytes treated with periostin were more migratory. Periostin production was also increased in HDM exposed mice as well as in cultured pericytes treated with IL-13. Conclusion: Periostin is produced by pericytes in response to TGF-β or IL-13, and periostin plays a key role in inducing pericyte migration. The increase in periostin expression in TGF-β or IL-13 treated pericytes suggests that IL-13 may trigger periostin production in pericytes whilst TGF-β modulates periostin expression to promote pericyte migration in the context of tissue fibrosis.
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骨膜素调节纤维细胞功能以促进肌纤维细胞分化和肺纤维化。
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