PTX3

What is PTX3 protein?

PTX3 (pentraxin 3) gene is a protein coding gene which situated on the long arm of chromosome 3 at locus 3q25. Pentraxin 3(PTX3) is the prototypic member of the long pentraxin family sharing the C-terminal domain with short pentraxins and containing a unique N-terminal domain. Pentraxin 3 is produced and released at inflammatory sites by diverse cell types including monocytes/macrophages, endothelial cells, vascular smooth muscle cells, fibroblasts, and adipocytes. The PTX3 protein is consisted of 381 amino acids and its molecular mass is approximately 42.0 kDa.

What is the function of PTX3 protein?

The expression of this protein is induced by inflammatory cytokines in response to inflammatory stimuli in several mesenchymal and epithelial cell types, particularly endothelial cells and mononuclear phagocytes. The protein promotes fibrocyte differentiation and is involved in regulating inflammation and complement activation. It also plays a role in angiogenesis and tissue remodeling. The protein serves as a biomarker for several inflammatory conditions.

Fig1. A schematic diagram illustrates the proposed model. Astrocytic Cebpd promotes fibroblast. (Monika Zajkowska, 2023)

PTX3 Related Signaling Pathway

PTX3 is involved in the development of inflammation by regulating the TLR4/NF-κB signaling pathway, IL-1/TNF-α signaling pathway, and MAPK signaling pathway. In JNK/c-Jun signaling pathway, PI3K/Akt signaling pathway, Wnt/β-Catenin signaling pathway, PTX3 can participate in the regulation of cell proliferation, growth and other activities.

Fig2. A schematic diagram illustrates the proposed model. Astrocytic Cebpd promotes fibroblast migration to form fibrotic scars through Ptx3 secretion. (Shao-Ming Wang, 2023)

PTX3 Related Diseases

PTX3 protein has been implicated in a variety of diseases, including tumors, inflammatory diseases, infectious diseases, cardiovascular diseases, and more. There may even be a link to neurodegenerative diseases such as Alzheimer's and Parkinson's.

Bioapplications of PTX3

Due to its important role in inflammation and infection, PTX3 is considered as a biomarker for many diseases. For example, high levels of PTX3 expression are associated with diseases such as atherosclerosis, rheumatoid arthritis, and systemic lupus erythematosus. Using recombinant PTX3 technology, novel vaccines can be developed.

Case study 1: Yao Li, 2023

Myasthenia gravis (MG) is an autoantibodies-mediated autoimmune disease with the complications of neuromuscular junction transmission. In this study, the researchers aimed to investigate the molecular regulatory roles of pentaxin 3 (PTX3) in patients and in animal model with MG and to explore its underlying mechanism.

Patients with MG were identified and enrolled at our designated hospital and animal model was utilized for the proposed study. Enzyme-linked immunosorbent assay (ELISA) kit were used to quantify the IL-1β, IL-6, INF-γ, IL-17, TNF-α, anti-TAChR IgG/IgG1/IgG2b/IgG2c levels. The expression level of mRNA and protein product of PTX3 increased in the mice with MG. PTX3 promoted inflammation, pyroptosis in patients as well as in the MG mouse model. In addition, PTX3 induced the STAT3/NLRP3 inflammasome and promoted gene synthesis of STAT3.

Fig1. PTX3 promoted inflammation level using in vitro model. PTX3 mRNA expression.

Fig2. Full-length GSDMD (Fl-GSDMD) and N-terminal domain of GSDMD (N-GSDMD) protein expression in vitro model by down-regulation of PTX3.

Case study 2: Relber A Gonçales, 2022

The long pentraxin PTX3 (pentraxin 3) has emerged as a component of humoral innate immunity with essential functions in the resolution of inflammation, but its role during granuloma formation is unknown. To evaluate PTX3 as a modulator of pathogenic signals involved in granuloma formation and inflammation in sarcoidosis, peripheral blood mononuclear cells obtained from patients with sarcoidosis harboring loss-of-function genetic variants and gene-deleted mice were used to assess the role of PTX3 in experimental models of granuloma formation in vitro and in vivo.

The researchers have identified a molecular link between PTX3 deficiency and the pathogenic amplification of complement activation to promote granuloma formation. Mechanistically, PTX3 deficiency licensed the complement component C5a-mediated activation of the metabolic checkpoint kinase mTORC1. The results identify PTX3 as a pivotal molecule that regulates complement-mediated signaling cues in macrophages to restrain granulomatous inflammation and highlight the therapeutic potential of this signaling axis in targeting granuloma formation in sarcoidosis.

Fig3. Immunofluorescence for C3b/iC3b/C3c in granulomas from WT and Ptx3-/- mice on Day 4 after sodA bead embolization and treatment with rPTX3 (recombinant PTX3) or PBS (representative of three independent experiments).

Fig4. Concentrations of glucose and lactate in lung supernatants from WT and Ptx3-/- mice on Day 4 after sodA bead embolization and treatment with PMX53 or PBS.

PTX3 has several biochemical functions, for example, (1->3)-beta-D-glucan binding,complement component C1q binding,virion binding. Some of the functions are cooperated with other proteins, some of the functions could acted by PTX3 itself. We selected most functions PTX3 had, and list some proteins which have the same functions with PTX3. You can find most of the proteins on our site.

PTX3 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with PTX3 here. Most of them are supplied by our site. Hope this information will be useful for your research of PTX3.