Gpx3, glutathione peroxidase 3, is a selenoprotein and the only extracellular GPx in a family of oxidoreductases. It catalyzes the detoxification of hydro-and soluble lipid hydroperoxides by reduced glutathione, playing a crucial role in the antioxidant defense system. It is involved in maintaining redox balance, which is essential for normal cell function and survival [2].

In cancer research, conditional knockout of Gpx3 in AT2 cells suppressed lung metastasis in spontaneous metastatic models, revealing its role in promoting pre-metastatic niche formation in lung metastasis [1]. In ovarian cancer, knockdown of Gpx3 in ID8 cells abrogated clonogenicity and intraperitoneal tumor development in vivo, and in OVCAR3 cells, loss of Gpx3 led to decreased gene expression patterns related to pro-tumorigenic signaling pathways [4].

In cardiomyocytes, Gpx3 suppression increased ROS levels, induced apoptosis, and promoted autophagy [3]. In a murine model of pulmonary artery banding, GPx3-deficient mice showed enhanced adverse right ventricular remodeling and signs of RV dysfunction [5].

In chronic kidney disease models, down-regulation of Gpx3 in renal tubular epithelium led to an oxidatively stressed extracellular microenvironment, driving interstitial fibroblast activation and proliferation [6].

In conclusion, Gpx3 is vital for antioxidant defense and redox balance. Gene knockout models, especially in cancer, cardiomyocyte, and right ventricle-related disease models, have revealed its role in tumor progression, cell apoptosis, autophagy, and organ-specific remodeling. These studies provide insights into disease mechanisms and potential therapeutic targets related to Gpx3 [1,3,4,5,6].