NGF/TrkA-mediated Kidins220/ARMS signaling activated in the allergic airway challenge in mice
NGF/TrkA-mediated Kidins220/ARMS signaling activated in the allergic airway challenge in mice
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NGF/TrkA 介导的 Kidins220/ARMS 信号在小鼠过敏性气道挑战中激活
DOI：
10.1016/j.anai.2010.08.006
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发表时间：
2010-10-01
影响因子：
5.9
通讯作者：
Zhang, Baohui
中科院分区：
文献类型：
--
作者：
Ni, Xiuqin;Li, Xing;Zhang, Baohui
工作背景：神经生长因子（NGF）及其高亲和力受体酪氨酸激酶受体A（TrkA）参与哮喘的发病机制。目的：探讨蛋白激酶D（PKD）的新型跨膜底物-富含锚蛋白的跨膜蛋白（ARMS）是否参与了哮喘的发病过程方法：采用卵白蛋白吸入法建立BALB/c小鼠哮喘模型。通过向小鼠施用抗-NGF或抗-TrkA抗体来评估NGF和TrkA在过敏性气道激发中对Kidins 220/ARMS的作用。苏木精-伊红染色观察支气管和肺组织的病理变化;计数支气管肺泡灌洗液（BALF）中的炎性细胞;免疫荧光法观察BALF细胞中ARMS和TrkA的共表达。结果：荧光显微镜下观察到Kidins 220和TrkA在哮喘小鼠BALF细胞膜上共表达。与对照动物的表达相比，过敏原激发后，Kidins 220/ARMS、CrkL、NGF和TrkA在肺中过表达。结论：Kidins 220/ARMS通过NGF-TrkA信号通路参与哮喘的发病，可能是哮喘发病的一个新机制。Ann Allergy Asthma Immunol.2010;105：299-306.
Background: Nerve growth factor (NGF), combined with its high-affinity receptor tyrosine kinase receptor A (TrkA), has been reported to be involved in the pathogenesis of asthma.Objective: To investigate whether the downstream protein ankyrin-rich membrane spanning (ARMS), a novel transmembrane substrate of protein kinase D (Kidins220), is activated in the pathogenesis of asthma.Methods: The asthmatic model was established by the inhalation of ovalbumin in BALB/c mice. The effects of NGF and TrkA on Kidins220/ARMS in an allergic airway challenge were assessed by administering anti-NGF or anti-TrkA antibody to the mice. Pathologic changes in the bronchi and lung tissues were examined by means of hematoxylin and eosin staining; the inflammatory cells in the bronchoalveolar lavage fluid (BALF) were counted; and co-expression of ARMS and TrkA in BALF cells was observed by means of immunofluorescence. In addition, Kidins220/ARMS, CrkL, NGF, TrkA protein, and Kidins220 messenger RNA levels were determined using Western blot or quantitative reverse transcription-polymerase chain reaction.Results: Using fluorescence microscopy, we found that Kidins220 and TrkA were co-expressed on the membranes of the BALF cells of asthmatic mice. Compared with expression in control animals, Kidins220/ARMS, CrkL, NGF, and TrkA were overexpressed in the lungs after allergen challenge. Moreover, after the mice were treated with anti-NGF or anti-TrkA, the Kidins220/ARMS levels and allergen-induced airway inflammation decreased.Conclusions: These results suggest that Kidins220/ARMS partly participates in the pathogenesis of asthma through the NGF-TrkA signaling pathway, possibly representing a new mechanism in asthma. Ann Allergy Asthma Immunol. 2010;105:299-306.