Glrx, also known as glutaredoxin, is a crucial oxidoreductase enzyme. It plays a central role in cellular redox chemistry, regulating redox homeostasis by performing deglutathionylation, a post-translational modification involving the conjugation of glutathione to protein thiols [4,6]. Glrx is involved in multiple biological pathways, such as those related to inflammation, cell proliferation, and apoptosis, and is of great biological importance in various physiological and pathological processes [2,3,5,7]. Genetic models, like knockout (KO) and conditional knockout (CKO) mouse models, have been valuable in studying Glrx.

In acute lung injury mouse models, the expression of the deglutathionylation enzyme Grx1 (a form of Glrx) is decreased. Grx1 KO and Grx1fl/flLysMcre mice show significant relief of hyperoxia-or LPS-induced acute lung injury, indicating the protective role of Grx1-regulated S-glutathionylation in macrophages [1]. In gefitinib-resistant NSCLC cells, GLRX is upregulated, and its inhibition enhances the effects of gefitinib on cell proliferation, apoptosis, and cell cycle arrest via the EGFR/FoxM1 signaling pathway [3]. In liver fibrosis, Glrx depletion exacerbates fibrosis, while overexpression inhibits it. Pirfenidone, an anti-lung fibrosis drug, inhibits HSC activation and liver fibrosis in a GLRX-dependent manner by deglutathionylating Smad3 [5].

In conclusion, Glrx plays essential roles in maintaining redox homeostasis and is involved in various biological processes. The KO/CKO mouse models have significantly contributed to understanding its role in diseases such as acute lung injury, NSCLC, and liver fibrosis, providing potential therapeutic targets for these conditions.