PRDX1 negatively regulates bleomycin-induced pulmonary fibrosis via inhibiting the epithelial-mesenchymal transition and lung fibroblast proliferation in vitro and in vivo

Abstract

Background Pulmonary fibrosis is a major category of end-stage changes in lung diseases, characterized by lung epithelial cell damage, proliferation of fibroblasts, and accumulation of extracellular matrix. Peroxiredoxin 1 (PRDX1), a member of the peroxiredoxin protein family, participates in the regulation of the levels of reactive oxygen species in cells and various other physiological activities, as well as the occurrence and development of diseases by functioning as a chaperonin. Methods Experimental methods including MTT assay, morphological observation of fibrosis, wound healing assay, fluorescence microscopy, flow cytometry, ELISA, western blot, transcriptome sequencing, and histopathological analysis were used in this study. Results PRDX1 knockdown increased ROS levels in lung epithelial cells and promoted epithelial-mesenchymal transition (EMT) through the PI3K/Akt and JNK/Smad signalling pathways. PRDX1 knockout significantly increased TGF-β secretion, ROS production, and cell migration in primary lung fibroblasts. PRDX1 deficiency also increased cell proliferation, cell cycle circulation, and fibrosis progression through the PI3K/Akt and JNK/Smad signalling pathways. BLM treatment induced more severe pulmonary fibrosis in PRDX1-knockout mice, mainly through the PI3K/Akt and JNK/Smad signalling pathways. Conclusions Our findings strongly suggest that PRDX1 is a key molecule in BLM-induced lung fibrosis progression and acts through modulating EMT and lung fibroblast proliferation; therefore, it may be a therapeutic target for the treatment of BLM-induced lung fibrosis.

DDAH1 recruits peroxiredoxin 1 and sulfiredoxin 1 to preserve its activity and regulate intracellular redox homeostasis

“…Although PRDX1 is primarily a H 2 O 2 scavenging enzyme, its knockdown or overexpression significantly affected the DHE fluorescence intensity in H 2 O 2 -treated cells and CCl 4 -challenged livers. The negative regulation on superoxide levels by PRDX1 has also been reported in bleomycin-treated BEAS-2B cells and lungs of mice [ 45 ]. It has been reported that H 2 O 2 can increase superoxide levels and induce mitochondrial dysfunction in HUVEC cells [ 46 ].…”

The direct binding of bioactive peptide Andersonin-W1 to TLR4 expedites the healing of diabetic skin wounds

“…The protein supernatants were collected after centrifugation (14,000 g , 20 min, 4 °C) and quantified using the Bradford method (BCA protein analysis kit, Meilun, Dalian, China). Western blotting was performed to detect the effects of AW1 on the nuclear factor‐κB (NF-κB) signaling pathway and TLR4/NF-κB molecular axis according to previous studies [ 3 , 39 ]. Primary antibodies, including GAPDH, Iκb, P-iκb, P65, and P-P65 (Affinity; China, 1:1 000), were used for western blotting according to the provided instructions.…”