A novel role of peroxiredoxin 2 in diabetic kidney disease progression by activating the classically activated macrophages

Abstract

Diabetic kidney disease (DKD) is the main cause of death due to diabetes mellitus (DM). Due to the complexity of the onset, it is difficult to achieve accurate prevention and treatment. The classically activated macrophages (M1) polarization is a crucial proinflammatory mechanism in DKD, while the interaction and cascade effects of oxidative stress and inflammatory response remain to be elucidated. A urine proteomic analysis of DM patients indicated that peroxiredoxin 2 (PRDX2) had the higher abundance in DKD. We recently found that PRDX of parasitic protozoa Entamoeba histolytica, which was similar to human PRDX2 in amino acid sequence and spatial structure, could activate the inflammatory response of macrophages through toll like receptor 4 (TLR4). Hence, our study was designed to explore the role of PRDX2 in chronic inflammation during DKD. Combined with in vivo and in vitro experiments, results showed that the PRDX2 was positively correlated with DKD progression and upregulated by high glucose or recombinant tumor necrosis factor-α in renal tubular epithelial cells; Besides, recombinant PRDX2 could promote macrophages M1 polarization, enhance the migration and phagocytic ability of macrophages through TLR4. In summary, our study has explored the novel role of PRDX2 in DKD to provide basis for further researches on the diagnosis and treatment of DKD.