The overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis

Abstract

BackgroundAcute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is life-threatening. Several serum biomarkers, such as Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), are clinically used for evaluating AE-IPF, but these biomarkers are not adequate for establishing an early and accurate diagnosis of AE-IPF. Recently, the protective roles of the members of the peroxiredoxin (PRDX) family have been reported in IPF; however, the role of PRDX4 in AE-IPF is unclear.MethodsSerum levels of PRDX4 protein, KL-6, SP-D and lactate dehydrogenase (LDH) in 51 patients with stable IPF (S-IPF), 38 patients with AE-IPF and 15 healthy volunteers were retrospectively assessed using enzyme-linked immunosorbent assay. Moreover, as an animal model of pulmonary fibrosis, wild-type (WT) and PRDX4-transgenic (Tg) mice were intratracheally administered with bleomycin (BLM, 2 mg/kg), and fibrotic and inflammatory changes in lungs were evaluated 3 weeks after the intratracheal administration.ResultsSerum levels of PRDX4 protein, KL-6, SP-D and LDH in patients with S-IPF and AE-IPF were significantly higher than those in healthy volunteers, and those in AE-IPF patients were the highest among the three groups. Using receiver operating characteristic curves, area under the curve values of serum PRDX4 protein, KL-6, SP-D, and LDH for detecting AE-IPF were 0.873, 0.698, 0.675, and 0.906, respectively. BLM-treated Tg mice demonstrated aggravated histopathological findings and poor prognosis compared with BLM-treated WT mice. Moreover, PRDX4 expression was observed in alveolar macrophages and lung epithelial cells of BLM-treated Tg mice.ConclusionsPRDX4 is associated with the aggravation of inflammatory changes and fibrosis in the pathogenesis of IPF, and serum PRDX4 may be useful in clinical practice of IPF patients.

Overexpression of PRDX4 Modulates Tumor Microenvironment and Promotes Urethane-Induced Lung Tumorigenesis

“…Another study found that PRDXs released by cancer cells can mediate osteoclastogenesis [ 14 ], a process mainly performed by macrophages. Our recent study demonstrated that PRDX4 overexpression was associated with the aggravation of inflammation in idiopathic pulmonary fibrosis [ 49 ]. Briefly, antioxidant therapy should be approached with caution, even in inflammatory disease, and the treatment should be based on the administration of certain antioxidants and for specified inflammation.…”

A Systematic Review of the Prognostic Significance of the Body Mass Index in Idiopathic Pulmonary Fibrosis

“…Among them, 1220 were excluded because they were either duplicates or irrelevant. After a full-text review of the remaining 37 articles, one was further excluded because it did not fulfill the inclusion criteria, thus leaving 36 studies (9958 IPF patients, 78% males) for final analysis [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ] ( Figure 1 ). Fourteen studies were conducted in Japan [ 22 , 27 , 29 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 43 , 45 , 50 , 51 ], nine in the USA [ 21 , 25 , 31 , …”

Bioinformatics Analysis of Common Genetic and Molecular Traits and Association of Portal Hypertension with Pulmonary Hypertension

“…Under normal physiological conditions, MDM2 can degrade the P53 proteasome to stabilize it at a low level, but under harmful stimulation, the reduced binding of MDM2 to P53 can promote the high level of P53 [ 35 ]. PRDX4 is a peroxidase that scavenges free radicals, but overexpression leads to cell proliferation [ 36 , 37 ]. Some scholars have stated that overexpression of PRDX4 does not show antioxidation, but induces inflammation and aggravates the development of pulmonary fibrosis [ 38 ].…”