mTORC1型
血管生成
车站3
呼吸上皮
卵清蛋白
STAT蛋白
信号转导
细胞生物学
下调和上调
转录因子
生物
免疫学
癌症研究
上皮
PI3K/AKT/mTOR通路
免疫系统
生物化学
基因
遗传学
作者
Xu Chen,Manli Miao,Meng Zhou,Jie Chen,Dapeng Li,Ling Zhang,Anjiang Sun,Minglong Guan,Zixi Wang,Ping Liu,Shengquan Zhang,Xiaojun Zha,Xiaoning Fan
标识
DOI:10.1038/s41419-021-04055-2
摘要
Angiogenesis is a key characteristic of asthma airway remodeling. By releasing cationic granule proteins, such as major basic protein (MBP), activated eosinophils play a prominent role in asthma, but the underlying mechanisms are still not fully understood. In this study, we demonstrated that fibroblast growth factor-binding protein 1 (FGFBP1) was dramatically upregulated in airway epithelial cell lines treated by poly-L-arginine (PLA), a mimic of MBP. Elevated FGFBP1 expression was also detected in asthma clinical samples, as well as in ovalbumin (OVA)-induced chronic asthma mouse models. PLA enhanced FGFBP1 expression through activation of the mechanistic target of rapamycin complex 1-signal transducer and activator of transcription 3 (mTORC1-STAT3) signaling pathway. STAT3 transactivated FGFBP1 by directly binding to the promoter of the FGFBP1 gene. Furthermore, we identified that FGFBP1 secreted by PLA-treated airway epithelial cells served as a proangiogenesis factor. Lastly, we found the mTORC1-STAT3-FGFBP1 signaling pathway was activated in an OVA-induced chronic asthma model with airway remodeling features. Rapamycin treatment alleviated respiratory symptoms and reduced angiogenesis in asthmatic mice. Therefore, activation of the mTORC1-STAT3-FGFBP1 pathway in the airway epithelium contributes to the progress of angiogenesis and should be targeted for the treatment of asthma.
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