Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma.
Pericytes contribute to airway remodeling in a mouse model of chronic allergic asthma.
复制标题
DOI：
10.1152/ajplung.00286.2014
复制
发表时间：
2015-04-01
期刊：
影响因子：
--
通讯作者：
Fuxe J
中科院分区：
文献类型：
--
作者：
Johnson JR;Folestad E;Rowley JE;Noll EM;Walker SA;Lloyd CM;Rankin SM;Pietras K;Eriksson U;Fuxe J
肌成纤维细胞堆积、上皮下纤维化和血管重构是慢性哮喘的并发症，但其机制尚不清楚。血小板衍生生长因子(PDGFs)调节多种间充质细胞的命运和功能，并被认为是肺纤维化的介质。然而，目前尚不清楚血小板衍生生长因子-BB信号通过血小板衍生生长因子受体β在慢性哮喘的气道重塑中是否起作用。在本研究中，我们使用选择性的血小板衍生生长因子受体β抑制剂(CP-673451)来研究血小板衍生生长因子受体β信号在尘螨诱导的慢性过敏性哮喘小鼠模型的气道重塑和肺功能障碍中的作用。出乎意料的是，我们发现，在慢性空气变应原暴露的背景下，药物抑制PDGFRβ信号导致加剧肺功能障碍和气道平滑肌增厚。进一步的研究表明，小鼠对空气变应原攻击的炎症反应与PDGF-BB表达减少和呼吸道微血管周细胞丢失有关。同时，周细胞标记阳性的细胞聚集在慢性炎症的呼吸道上皮下区。在用CP-673451治疗的动物中，这一过程加剧了。结果提示，PDGFBB/PDGFFRβ信号转导通路的紊乱和周细胞在气道壁的聚集可能参与了慢性过敏性哮喘的气道重构。
Myofibroblast accumulation, subepithelial fibrosis, and vascular remodeling are complicating features of chronic asthma, but the mechanisms are not clear. Platelet-derived growth factors (PDGFs) regulate the fate and function of various mesenchymal cells and have been implicated as mediators of lung fibrosis. However, it is not known whether PDGF-BB signaling via PDGFRβ, which is critical for the recruitment of pericytes to blood vessels, plays a role in airway remodeling in chronic asthma. In the present study, we used a selective PDGFRβ inhibitor (CP-673451) to investigate the role of PDGFRβ signaling in the development of airway remodeling and lung dysfunction in an established mouse model of house dust mite-induced chronic allergic asthma. Unexpectedly, we found that pharmacological inhibition of PDGFRβ signaling in the context of chronic aeroallergen exposure led to exacerbated lung dysfunction and airway smooth muscle thickening. Further studies revealed that the inflammatory response to aeroallergen challenge in mice was associated with decreased PDGF-BB expression and the loss of pericytes from the airway microvasculature. In parallel, cells positive for pericyte markers accumulated in the subepithelial region of chronically inflamed airways. This process was exacerbated in animals treated with CP-673451. The results indicate that perturbed PDGF-BB/PDGFRβ signaling and pericyte accumulation in the airway wall may contribute to airway remodeling in chronic allergic asthma.
登录
查看更多内容
影响因子：
12.4
作者：
CHANEZ, P;VIGNOLA, M;BOUSQUET, J
通讯作者：
BOUSQUET, J
DOI：
10.1164/rccm.200308-1094oc
发表时间：
2004-02-01
影响因子：
24.7
作者：
Johnson, JR;Wiley, RE;Jordana, M
通讯作者：
Jordana, M
影响因子：
6
作者：
Lin, Shuei-Liong;Kisseleva, Tatiana;Duffield, Jeremy S.
通讯作者：
Duffield, Jeremy S.
影响因子：
14.2
作者：
Al-Muhsen, Saleh;Johnson, Jill R.;Hamid, Qutayba
通讯作者：
Hamid, Qutayba
影响因子：
12.4
作者：
Humbert, M.;de Blay, F.;Chanez, P.
通讯作者：
Chanez, P.