Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
ASST Spedali Civili di Brescia, Brescia, Italy.
Front Immunol. 2021 Feb 18;12:617671. doi: 10.3389/fimmu.2021.617671. eCollection 2021.
Pulmonary fibrosis is a progressive scarring disease of the lungs, characterized by inflammation, fibroblast activation, and deposition of extracellular matrix. The long pentraxin 3 (PTX3) is a member of the pentraxin family with non-redundant functions in innate immune responses, tissue repair, and haemostasis. The role played in the lungs by PTX3 during the fibrotic process has not been elucidated. In this study, the impact of PTX3 expression on lung fibrosis was assessed in an intratracheal bleomycin (BLM)-induced murine model of the disease applied to wild type animals, transgenic mice characterized by endothelial overexpression and stromal accumulation of PTX3 (Tie2-PTX3 mice), and genetically deficient animals. Our data demonstrate that PTX3 is produced during BLM-induced fibrosis in wild type mice, and that PTX3 accumulation in the stroma compartment of Tie2-PTX3 mice limits the formation of fibrotic tissue in the lungs, with reduced fibroblast activation and collagen deposition, and a decrease in the recruitment of the immune infiltrate. Conversely, -null mice showed an exacerbated fibrotic response and decreased survival in response to BLM treatment. These results underline the protective role of endogenous PTX3 during lung fibrosis and pave the way for the study of novel PTX3-derived therapeutic approaches to the disease.
肺纤维化是一种肺部进行性瘢痕疾病，其特征为炎症、成纤维细胞活化和细胞外基质沉积。长 pentraxin 3（PTX3）是 pentraxin 家族的一员，在先天免疫反应、组织修复和止血中具有非冗余的功能。PTX3 在纤维化过程中在肺部中的作用尚未阐明。在这项研究中，在应用于野生型动物、PTX3 内皮过表达和基质积累的转基因小鼠（Tie2-PTX3 小鼠）以及基因缺失动物的博来霉素（BLM）诱导的肺部疾病的气管内 BLM 诱导的小鼠模型中，评估了 PTX3 表达对肺纤维化的影响。我们的数据表明，PTX3 在野生型小鼠的 BLM 诱导的纤维化中产生，并且 Tie2-PTX3 小鼠基质中 PTX3 的积累限制了肺部纤维组织的形成，成纤维细胞活化和胶原蛋白沉积减少，免疫浸润的募集减少。相反，-/- 小鼠在 BLM 治疗后表现出加重的纤维化反应和存活率降低。这些结果强调了内源性 PTX3 在肺纤维化过程中的保护作用，并为研究新型 PTX3 衍生的治疗方法铺平了道路。
