PTX3 Regulation of Inflammation, Hemostatic Response, Tissue Repair, and Resolution of Fibrosis Favors a Role in Limiting Idiopathic Pulmonary Fibrosis

Abstract

PTX3 is a soluble pattern recognition molecule (PRM) belonging to the humoral innate immune system, rapidly produced at inflammatory sites by phagocytes and stromal cells in response to infection or tissue injury. PTX3 interacts with microbial moieties and selected pathogens, with molecules of the complement and hemostatic systems, and with extracellular matrix (ECM) components. In wound sites, PTX3 interacts with fibrin and plasminogen and favors a timely removal of fibrin-rich ECM for an efficient tissue repair. Idiopathic Pulmonary Fibrosis (IPF) is a chronic and progressive interstitial lung disease of unknown origin, associated with excessive ECM deposition affecting tissue architecture, with irreversible loss of lung function and impact on the patient’s life quality. Maccarinelli et al. recently demonstrated a protective role of PTX3 using the bleomycin (BLM)-induced experimental model of lung fibrosis, in line with the reported role of PTX3 in tissue repair. However, the mechanisms and therapeutic potential of PTX3 in IPF remained to be investigated. Herein, we provide new insights on the possible role of PTX3 in the development of IPF and BLM-induced lung fibrosis. In mice, PTX3-deficiency was associated with worsening of the disease and with impaired fibrin removal and subsequently increased collagen deposition. In IPF patients, microarray data indicated a down-regulation of PTX3 expression, thus suggesting a potential rational underlying the development of disease. Therefore, we provide new insights for considering PTX3 as a possible target molecule underlying therapeutic intervention in IPF.

Lateral Mesoderm-Derived Mesenchymal Stem Cells With Robust Osteochondrogenic Potential and Hematopoiesis-Supporting Ability

“…Increased protease (MMP/TIMP) and PTX3 expression was found in LM-MSCs and BMSCs compared to LM cells in RNA-Seq, which was further confirmed by RT-PCR assays ( Supplementary Figure S7 ). Upregulation of these genes may be involved in the migration, invasion, ECM remodeling, and angiogenesis properties of LM-MSCs ( Lu et al, 2010 ; Cappuzzello et al, 2016 ; Doni et al, 2021 ). In addition, RNA-Seq data indicated that LM-MSCs highly expressed HOX9-13 genes, which was consistent with the qRT-PCR results described above ( Figure 6C ).…”

Activation of an injury-associated transient progenitor state in the epicardium is required for zebrafish heart regeneration

“…We next focused on the markers of the 3 dpa-specific cluster 5 to characterize its identity. This cluster is enriched with pro-regenerative ECM and related genes including pentraxin 3 long a ( ptx3a ), collagen type XII alpha 1b ( col12a1b ), myristoylated alanine-rich protein kinase C substrate b ( marcksb ), and fibronectin 1a ( fn1a ) (Figures 3E and S4) 41, 42, 43, 44, 45, 46, 47 . In addition to the injury-induced epicardial expression of fn1a that is required for heart regeneration 41 , collagen XII (Col XII) deposition was reported to be boosted in both the epicardium and wounded tissues after cryoinjury in zebrafish 42 .…”

“…Col XII is also an axon growth-promoting ECM that helps zebrafish spinal cord regeneration 43, 44 . Ptx3 is a secreted humoral innate immunity factor that orchestrates inflammation and tissue repair 45 . Besides the interactions with pathogens and complement molecules, Ptx3 also interacts with ECM components, such as fibrin and plasminogen, to promote a timely removal of fibrotic ECM for efficient tissue repair 48, 49 .…”

Cytokine and Chemokine Retention Profile in COVID-19 Patients with Chronic Kidney Disease

“…Pentraxin 3 (PTX3) is an acute phase protein and a key component of immune humoral immunity rapidly synthetized by different cell types in response to microbial infection, tissue damage and different soluble factors such as TNF-α and IL-1. For its actions, PTX3 can be considered a humoral pattern recognition molecule that provides defence against infection playing several function in tissue repair [ 37 ]. In COVID-19, PTX3 has been proposed as a biomarker able to predict mortality at 28 days [ 38 , 39 ].…”