Laboratory of Tumor and Development Biology, GIGA-Cancer, University of Liege (ULiege), Liege, Belgium.
Department of Otorhinolaryngology Head and Neck Surgery, University of Liege (ULiege) and Centre Hospitalier Universitaire (CHU) Liege, Liege, Belgium.
Front Immunol. 2023 Jan 5;13:1067779. doi: 10.3389/fimmu.2022.1067779. eCollection 2022.
Asthma is characterized by morphological modifications of the airways (inflammation and remodelling) and bronchial hyperresponsiveness. Mechanisms linking these two key features of asthma are still poorly understood. ADAM28 (a disintegrin and metalloproteinase 28) might play a role in asthma pathophysiology. ADAM28 exists as membrane-bound and soluble forms and is mainly expressed by lymphocytes and epithelial cells.
ADAM28 mice and ADAM28 counterparts were sensitized and exposed to ovalbumin (OVA). Airway responsiveness was measured using the flexiVent system. After sacrifice, bronchoalveolar lavage (BAL) was performed and lungs were collected for analysis of airway inflammation and remodelling.
The expression of the soluble form of ADAM28 was lower in the lungs of OVA-exposed mice (as compared to PBS-exposed mice) and progressively increased in correlation with the duration of allergen exposure. In lungs of ADAM28 mice exposed to allergens, the proportion of Th2 cells among cells and the number of B cells were decreased. Bronchial responsiveness was lower in ADAM28 mice exposed to allergens and similar to the responsiveness of sham-challenged mice. Similarly, features of airway remodelling (collagen deposition, smooth muscle hyperplasia, mucous hyperplasia) were significantly less developed in OVA-exposed ADAM28 animals in sharp contrasts to ADAM28. In addition, we report the first evidence of ADAM28 RNA expression by lung fibroblasts and we unveil a decreased capacity of lung fibroblasts extracted from OVA-exposed ADAM28 mice to proliferate as compared to those extracted from OVA-exposed ADAM28 suggesting a direct contribution of this enzyme to the modulation of airway remodelling.
These results suggest that ADAM28 might be a key contributor to the pathophysiology of asthma.
哮喘的特征在于气道的形态学改变（炎症和重塑）和支气管高反应性。将这两个哮喘的关键特征联系起来的机制仍知之甚少。ADAM28（解整合素和金属蛋白酶 28）可能在哮喘病理生理学中发挥作用。ADAM28 存在膜结合和可溶性两种形式，主要由淋巴细胞和上皮细胞表达。
ADAM28 小鼠和 ADAM28 对照小鼠进行致敏和暴露于卵清蛋白（OVA）。使用 flexiVent 系统测量气道反应性。牺牲后，进行支气管肺泡灌洗（BAL）并收集肺组织，用于分析气道炎症和重塑。
OVA 暴露的小鼠（与 PBS 暴露的小鼠相比）肺组织中可溶性 ADAM28 的表达较低，并与过敏原暴露时间呈正相关逐渐增加。在暴露于过敏原的 ADAM28 小鼠的肺部，细胞中的 Th2 细胞比例和 B 细胞数量减少。暴露于过敏原的 ADAM28 小鼠的支气管反应性较低，与假处理的小鼠相似。同样，OVA 暴露的 ADAM28 动物的气道重塑特征（胶原沉积、平滑肌增生、粘液增生）明显发育不良，与 ADAM28 形成鲜明对比。此外，我们首次报道了肺成纤维细胞中 ADAM28 RNA 表达，并揭示了从 OVA 暴露的 ADAM28 小鼠中提取的肺成纤维细胞的增殖能力降低，与从 OVA 暴露的 ADAM28 中提取的细胞相比，这表明该酶直接参与了气道重塑的调节。
这些结果表明 ADAM28 可能是哮喘病理生理学的关键贡献者。
Zotero 插件
