Bevacizumab reduced auto-phosphorylation of VEGFR2 to protect HDM-induced asthma mice
Bevacizumab reduced auto-phosphorylation of VEGFR2 to protect HDM-induced asthma mice
复制标题
贝伐单抗降低 VEGFR2 的自身磷酸化以保护 HDM 诱导的哮喘小鼠
DOI：
10.1016/j.bbrc.2016.07.072
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发表时间：
2016-09-09
影响因子：
3.1
通讯作者：
Cai, Shaoxi
中科院分区：
文献类型：
--
作者：
Huang, Chaowen;Dong, Hangming;Cai, Shaoxi
血管内皮生长因子（VEFG）是一种主要的血管生成因子，参与胚胎发育和伤口愈合等正常生理过程以及癌症等疾病。最近的研究揭示了 VEGF 在炎症和免疫调节中的功能。哮喘是一种慢性气道炎症，其特征是气道上皮屏障功能障碍和免疫调节过程中辅助性 T (Th)1/Th2 失衡。我们假设 VEGF 在哮喘中发挥重要作用。利用屋尘螨提取物 (HDM) 诱导的小鼠哮喘模型，我们研究了贝伐单抗（一种人源化抗 VEGF 单克隆抗体）是否可以保护小鼠气道的上皮屏障。我们发现贝伐珠单抗可减少 HDM 引起的气道高反应性 (AHR) 和气道炎症。此外，HDM 暴露促进 VEGF 表达，并引起 AHR、上皮屏障破坏和气道炎症。贝伐单抗改善 AHR 和 Th2 细胞因子的释放，从而保护上皮屏障。我们的数据表明贝伐珠单抗可能是哮喘的新治疗策略。 (C) 2016 Elsevier Inc. 保留所有权利。
Vascular endothelial growth factor (VEFG) is a major angiogenic factor involved in both normal physiological processes, such as embryonic development and wound healing, and in diseases, like cancer. Recent studies have revealed the functions of VEGF in inflammation and immunoregulation. Asthma is a chronic inflammation of the airways characterized by airway epithelial barrier dysfunction and imbalance in T-helper (Th) 1/Th2 during immunoregulation. We hypothesized that VEGF plays an important role in asthma. Utilizing a house dust mite extract (HDM)-induced murine model of asthma, we investigated whether bevacizumab, a humanized anti-VEGF monoclonal antibody, could protect the epithelial barrier in murine airways. We found that bevacizumab reduced airway hyper-responsiveness (AHR) and airway inflammation induced by HDM. In addition, HDM exposure promoted expression of VEGF, and caused AHR, disruptions of the epithelial barrier, and airway inflammation. Bevacizumab ameliorated AHR and the release of Th2 cytokines, thereby protecting the epithelial barrier. Our data suggest that bevacizumab may be a new therapeutic strategy for asthma. (C) 2016 Elsevier Inc. All rights reserved.