Increased Expression of Angiopoietins and Tie2 in the Lungs of Chronic Asthmatic Mice
Increased Expression of Angiopoietins and Tie2 in the Lungs of Chronic Asthmatic Mice
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DOI：
10.1165/rcmb.2009-0330oc
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发表时间：
2011-03-01
影响因子：
6.4
通讯作者：
Agrawal, Devendra K.
中科院分区：
文献类型：
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作者：
Makinde, Toluwalope O.;Agrawal, Devendra K.
血管生成素 (Ang) 1 和 Ang2 是 Tie2 酪氨酸激酶受体 (Tie2) 的配体。据报道，哮喘患者诱导痰中 Ang1 和 Ang2 水平升高，且 Ang2 水平与气道阻塞的严重程度呈正相关。尽管研究表明在某些病理条件下 Tie2 介导的非血管细胞调节，但目前对哮喘中 Tie2 信号传导的了解仅限于脉管系统。我们检查了 Ang1、Ang2、血管内皮生长因子 (VEGF) 和 Tie2 的表达模式及其与卵清蛋白 (OVA) 致敏和 OVA 攻击的气道高反应性小鼠肺部气道重塑程度的相关性。 OVA致敏和攻击后从Balb/c小鼠中分离肺组织。使用苏木精和曙红、高碘酸希夫染色和三色染色来显示肺部病理学。使用免疫荧光、Western blot、ELISA 和实时 PCR 检查 Ang1、Ang2、VEGF 和 Tie2 的表达。在正常小鼠的肺中，仅在血管中检测到Tie2表达。然而，在 OVA 致敏和 OVA 攻击小鼠的肺中，除了肺血管中的组成型表达外，Tie2 在气道上皮细胞和巨噬细胞子集中也大量表达。 Tie2 表达的增加与气道重塑的严重程度相关。巨噬细胞和气道上皮细胞仅在过敏模型中表达 Ang2 和 VEGF。过敏模型中 Ang1 呈组成型表达，mRNA 水平下降。总之，过敏性气道上皮和肺泡巨噬细胞中 Tie2 和 Ang2 表达的增加与气道重塑的严重程度相关。
Angiopoietin (Ang) 1 and Ang2 are ligands for Tie2 tyrosine kinase receptor (Tie2). Elevated levels of Ang1 and Ang2 in induced sputum of patients with asthma have been reported, with a positive correlation of Ang2 levels with the severity of airway occlusion. Although studies have shown Tie2-mediated regulation of nonvascular cells in some pathological conditions, current knowledge on Tie2 signaling in asthma is limited to the vasculature. We examined the expression pattern of Ang1, Ang2, vascular endothelial growth factor (VEGF), and Tie2 and their correlation with the degree of airway remodeling in the lung of ovalbumin (OVA)-sensitized and OVA-challenged mice with airway hyperresponsiveness. Lung tissues were isolated from Balb/c mice after OVA sensitization and challenge. Hematoxylin and eosin, periodic acid-Schiff, and trichrome staining were used to show the lung pathology. The expression of Ang1, Ang2, VEGF, and Tie2 was examined using immunofluorescence, Western blot, ELISA, and real-time PCR. In the lung of normal mice, Tie2 expression was detected only in the blood vessels. However, in the lung of OVA-sensitized and OVA-challenged mice, Tie2 was abundantly expressed in airway epithelial cells and in a subset of macrophages in addition to constitutive expression in pulmonary vessels. The increase in Tie2 expression correlated with the severity of airway remodeling. Macrophages and airway epithelial cells express Ang2 and VEGF only in allergic models. Ang1 was constitutively expressed, with a decrease in mRNA level in allergic models. In conclusion, increased expression of Tie2 and Ang2 in allergic airway epithelium and alveolar macrophages correlates with the severity of airway remodeling.