Division of Respiratory and Allergy, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, 170 Jomaru-ro, Wonmi-gu, Bucheon, Gyeonggi-do, 14584, Republic of Korea.
Lung. 2018 Dec;196(6):681-689. doi: 10.1007/s00408-018-0159-x. Epub 2018 Sep 4.
Annexin A5 (ANXA5) has a potential role in cellular signal transduction, inflammation, and fibrosis. However, the exact role of ANXA5 in asthma remains to be clarified. The aims of the present study were to investigate ANXA5 protein expression in a mouse model of asthma and pollutant exposure and to elucidate the relationships between clinical variables and plasma ANXA5 levels in patients with asthma.
A murine model of asthma induced by ovalbumin (OVA) and titanium dioxide (TiO) nanoparticles has been established using BALB/c mice, and we examined ANXA5 expression and lung fibrosis using this model. Moreover, we also compared ANXA5 plasma levels in patients with controlled vs. exacerbated asthma.
ANXA5 protein levels were lower in lung tissue from OVA + OVA mice than in control mice. Lung ANXA5, connective tissue growth factor (CTGF), and transforming growth factor β1 (TGF-β1) protein levels were higher in OVA + TiO-exposed mice than in control or OVA + OVA mice. Although Dermatophagoides pteronyssinus (Derp1) treatment increased lung ANXA5 protein levels in MRC-5 cells and A549 epithelial cells, it decreased lung ANXA5 levels in NHBE cells. Treatment with TiO nanoparticles increased lung ANXA5, CTGF, and TGF-β1 protein levels in MRC-5 cells, A549 epithelial cells, and NHBE cells. Plasma ANXA5 levels were lower in asthmatic patients than in healthy controls, and they were significantly enriched in patients with exacerbated asthma compared with those with controlled asthma (P < 0.05). ANXA5 levels were correlated with pulmonary function as assessed by spirometry.
Our results imply that ANXA5 plays a potential role in asthma pathogenesis and may be a promising marker for exacerbated bronchial asthma and exposure to air pollutants.
膜联蛋白 A5(ANXA5)在细胞信号转导、炎症和纤维化中具有潜在作用。然而,ANXA5 在哮喘中的确切作用仍有待阐明。本研究旨在探讨哮喘小鼠模型和污染物暴露中 ANXA5 蛋白的表达,并阐明哮喘患者临床变量与血浆 ANXA5 水平之间的关系。
采用 BALB/c 小鼠建立卵清蛋白(OVA)和二氧化钛(TiO)纳米颗粒诱导的哮喘小鼠模型,用该模型检测 ANXA5 表达和肺纤维化。此外,我们还比较了哮喘控制组和加重组患者的 ANXA5 血浆水平。
OVA+OVA 小鼠肺组织中的 ANXA5 蛋白水平低于对照组。OVA+TiO 暴露组小鼠肺组织中的 ANXA5、结缔组织生长因子(CTGF)和转化生长因子β1(TGF-β1)蛋白水平高于对照组或 OVA+OVA 组。尽管屋尘螨(Derp1)处理增加了 MRC-5 细胞和 A549 上皮细胞中的肺 ANXA5 蛋白水平,但降低了 NHBE 细胞中的肺 ANXA5 水平。TiO 纳米颗粒处理增加了 MRC-5 细胞、A549 上皮细胞和 NHBE 细胞中的肺 ANXA5、CTGF 和 TGF-β1 蛋白水平。哮喘患者的血浆 ANXA5 水平低于健康对照组,且在加重组哮喘患者中明显高于控制组(P<0.05)。ANXA5 水平与肺功能呈正相关,肺功能通过肺活量计评估。
我们的结果表明,ANXA5 在哮喘发病机制中具有潜在作用,可能是支气管哮喘加重和暴露于空气污染物的有前途的标志物。