Abstract

Background

Asthma characterized by airway hyperresponsiveness, inflammation, fibrosis, and angiogenesis. SRY-related HMG-box 18 (SOX18) is an important transcription factor involved in angiogenesis, tissue injury, wound-healing, and in embryonic cardiovascular and lymphatic vessels development. The role of angiogenic transcription factors, SOX18 and the related, prospero homeobox 1 (PROX1) and chicken ovalbumin upstream promoter transcription factor II (COUP-TFII), in asthma has had limited study.

Objective

In this study, we aimed to elucidate the role of SOX18 in the pathogenesis of bronchial asthma.

Methods

Plasma SOX18 protein was measured in control subjects, and subject with stable or exacerbated asthma. SOX18, PROX1, and COUP-TFII protein was measured by western blot, and immunohistochemistry in a murine model of ovalbumin-induced allergic asthma (OVA). SOX18, PROX1, and COUP-TFII protein was measured in lung human microvascular endothelial cells (HMVEC-L) and normal human bronchial epithelial (NHBE) cells treated with house dust mite (Der p1).

Results

Plasma SOX18 tended to be higher in subject with asthma compared to control subjects and increased more during exacerbation as compared to stable disease. In mice, OVA challenge lead to increased lung SOX18, PROX1, COUP-TFII, mucous gland hyperplasia and submucosal collagen. In NHBE cells, SOX18, PROX1 and COUP-TFII increased following Der p1 treatment. SOX18 protein increased in HMVEC-L following Der p1 treatment.

Conclusion

These results suggest that SOX18 may be involved in asthma pathogenesis and be associated with asthma exacerbation.

中文翻译：

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增强的血管生成转录因子 SOX18 与哮喘恶化有关

摘要

背景

以气道高反应性、炎症、纤维化和血管生成为特征的哮喘。SRY 相关 HMG-box 18 (SOX18) 是参与血管生成、组织损伤、伤口愈合以及胚胎心血管和淋巴管发育的重要转录因子。血管生成转录因子 SOX18 和相关的 prospero homeobox 1 (PROX1) 和鸡卵清蛋白上游启动子转录因子 II (COUP-TFII) 在哮喘中的作用研究有限。

客观的

在本研究中，我们旨在阐明 SOX18 在支气管哮喘发病机制中的作用。

方法

在对照受试者和患有稳定或恶化哮喘的受试者中测量血浆 SOX18 蛋白。在卵清蛋白诱导的过敏性哮喘 (OVA) 小鼠模型中，通过蛋白质印迹和免疫组织化学测量 SOX18、PROX1 和 COUP-TFII 蛋白。在用屋尘螨处理的人肺微血管内皮细胞 (HMVEC-L) 和正常人支气管上皮 (NHBE) 细胞中测量 SOX18、PROX1 和 COUP-TFII 蛋白 ( Der p 1)。

结果

与对照受试者相比，患有哮喘的受试者的血浆 SOX18 倾向于更高，并且与稳定的疾病相比，在恶化期间增加更多。在小鼠中，OVA 攻击导致肺 SOX18、PROX1、COUP-TFII、黏液腺增生和黏膜下胶原蛋白增加。在 NHBE 细胞中，SOX18、PROX1 和 COUP-TFII 在Der p 1 处理后增加。在Der p 1 处理后，HMVEC-L 中的 SOX18 蛋白增加。

结论

这些结果表明，SOX18 可能参与哮喘发病机制并与哮喘恶化有关。