Therapeutic potential of ISG20 in attenuating podocyte injury via inhibition of ferroptosis

, where the detrimental effects of ISG20 gene silencing could be mitigated by Fer-1 treatment in mouse podocytes under high glucose (HG) conditions. To further investigate the protective effects of ISG20, we administered two distinct vectors into diabetic mice: an adenovirus vector overexpressing ISG20 and a novel mRNA-loaded lipid nanoparticle (LNP) therapeutic vector expressing ISG20 mRNA. Both approaches effectively mitigated podocyte ferroptosis, alleviated podocyte injury, and reduced proteinuria in DKD. Similar results were also found in mice with adriamycin-induced nephropathy. Overall, this study establishes that ISG20 safeguards podocyte viability by suppressing ferroptosis, which extends ISG20's biological role. These findings suggest that ISG20 may be a potential therapeutic strategy for treating patients with proteinuric kidney disease.