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

• Published in: BMC pulmonary medicine Vol. 19; no. 1; p. 265
• Main Authors: Hanaka, Tetsuya, Kido, Takashi, Noguchi, Shingo, Yamada, Sohsuke, Noguchi, Hirotsugu, Guo, Xin, Nawata, Aya, Wang, Ke-Yong, Oda, Keishi, Takaki, Tsutomu, Izumi, Hiroto, Ishimoto, Hiroshi, Yatera, Kazuhiro, Mukae, Hiroshi
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.12.2019; BioMed Central; BMC
• Subjects: Acute exacerbation; Alveoli; Analysis; Animal models; Biomarkers; Bleomycin; Dehydrogenases; Development and progression; Diagnosis; Environmental health; Enzyme-linked immunosorbent assay; Enzymes; Epithelial cells; Fibrosis; Genetic engineering; Growth factors; Idiopathic pulmonary fibrosis; Immunoglobulins; Inflammation; L-Lactate dehydrogenase; Laboratories; Lactic acid; Lung diseases; Lungs; Macrophages; Medical prognosis; Mice; Peroxiredoxin; Peroxiredoxin 4; Protein D; Proteins; Pulmonary fibrosis; Pulmonology; Respiratory tract diseases; Rodents; Serum levels; Surface active agents; Surfactant protein D; Tomography; Trachea; Transgenic mice; Tumor necrosis factor-TNF; Japan; Taiwan; Mice; Peroxiredoxin 4; Acute exacerbation; Idiopathic pulmonary fibrosis
• ISSN: 1471-2466; 1471-2466
• DOI: 10.1186/s12890-019-1032-2

Acute 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. Serum 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. Serum 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. PRDX4 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.