Abstract
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 Ptx3−/− 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, Ptx3-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.
Highlights
Pulmonary fibrosis (PF) includes more than 200 different pathological conditions characterized by inflammation and scar tissue formation in the lungs
We investigated the impact of endogenous pentraxin 3 (PTX3) in a BLM-induced murine model of lung fibrosis
When compared to Wild type (WT) mice, fibrotic areas were significantly reduced in Tie2-PTX3 mice at all the time points investigated, close to the levels measured in untreated animals
Summary
Pulmonary fibrosis (PF) includes more than 200 different pathological conditions characterized by inflammation and scar tissue formation in the lungs. The most common type of PF is represented by the “Idiopathic Pulmonary Fibrosis” (IPF), whose etiology remains unknown. The incidence of IPF has increased over time in most countries worldwide, with approximately 50,000 new cases diagnosed each year in the U.S [2]. Starting symptoms of IPF, such as shortness of breath, dry hacking cough and fatigue, get significantly worse when the deposition of scar tissue augments, increases in stiffness and causes an irreversible loss of pulmonary functionality [3]. Despite the unknown cause(s) of IPF, aging (IPF is rare before 50 years of age), cigarette smoking, and genetic predisposition may represent relevant risk factors [4, 5].
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