Involvement of PRDX6 in the protective role of MANF in acute lung injury in rats

Aim/Purpose of the study: Acute lung injury (ALI) is a severe respiratory disease with high mortality, mainly due to overactivated oxidative stress and subsequent pyroptosis. Mesencephalic astrocyte-derived neurotrophic factor (MANF), an inducible secretory endoplasmic reticulum (ER) stress protein, inhibits lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the exact molecular mechanism remains unclear. Peroxiredoxin 6 (PRDX6), a peroxidase with a dual enzymatic function, is essential in regulating oxidative stress, which is closely associated with ALI. Furthermore, PRDX6 is an interacting protein of MANF. Therefore, this study aims to investigate the role of PRDX6 in the protective effect of MANF on ALI.Materials and Methods: In this study, we used LPS to establish the LPS-induced ALI model. Recombinant human MANF was administrated to wide-type (WT) and PRDX6 knockout (PRDX6-/-) rats.Results: In WT rats, MANF reversed the increases of PRDX6, ROS overgeneration, and pyroptosis-related protein-Gasdermin D (GSDMD) induced by LPS challenge. In PRDX6-/- rats, ROS generation, the protein level of GSDMD-N, and lung injury were not significantly decreased after human recombinant MANF administration in LPS-induced ALI.Conclusions: PRDX6 is involved in the protective role of MANF on ALI. It is a key target molecule for MANF to exert ALI inhibitory effects.