Prdx3-KO Mouse

Prdx3, peroxiredoxin 3, is a master regulator of mitochondrial oxidative stress. It acts as an efficient H2O2 scavenger, protecting cells from mitochondrial oxidative damage and apoptosis. It is involved in multiple biological pathways, such as those related to ferroptosis, liver fibrosis, and cell senescence, and is thus of great biological importance. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable for studying Prdx3.

In liver fibrosis, PRDX3 expression is negatively correlated with the disease state. AAV9-PRDX3 knockdown exacerbated hepatic fibrogenesis and HSC activation, while HSC-specific PRDX3 overexpression attenuated liver fibrosis. PRDX3 suppressed HSC activation via the mitochondrial reactive oxygen species (ROS)/TGF-β1/Smad2/3 pathway [1].

In intestinal ischemia/reperfusion (I/R) injury, PRDX3 expression decreased. Overexpression of PRDX3 significantly attenuated hypoxia/reoxygenation (H/R)-induced mitochondrial oxidative damage and apoptosis in Caco-2 cells. SIRT3-mediated deacetylation of PRDX3 at K253 alleviated mitochondrial oxidative damage and apoptosis [2].

In alveolar epithelial cells, YAP1 promoted Prdx3 expression. Forced expression of Prdx3 inhibited senescence and improved mitochondrial dysfunction in bleomycin-treated MLE-12 cells, while depletion of Prdx3 abrogated the protective effect of YAP1 in pulmonary fibrosis [3].

In conclusion, Prdx3 is crucial for maintaining mitochondrial function and cellular redox balance. Studies using KO/CKO mouse models have revealed its significant roles in liver fibrosis, intestinal I/R injury, and pulmonary fibrosis, providing potential therapeutic targets for these diseases.