biostudies-literatureDou QNational Natural Science Foundation of China439https://www.ebi.ac.uk/biostudies/studies/S-EPMC12686328biostudies-literatureUnknown82(1)Sepsis-associated acute kidney injury (SAKI) is a severe condition associated with high mortality and long-term complications. Currently, there is no effective strategy to halt AKI chronicization. Stress-induced senescence of renal tubular epithelial cells (RTECs) is a pivotal driving mechanism in the AKI-CKD transition. Previous scRNA-seq revealed that the expression of immediate early response gene 3 (IER3) was markedly upregulated in the senescent RTECs of patients with AKI and that the IER3⁺RTEC subpopulation exhibited diminished differentiation potential and impaired self-renewal capacity. However, the role of IER3 in RTEC stress-induced senescence following AKI remains unclear. In this study, we found that knockout of IER3 reduced mortality rates, alleviated renal injury, Cellular and molecular life sciences : CMLSIER3 drives the transition from sepsis-associated AKI to CKD by suppressing the mitochondrial translocation of PRDX5.PMC126863288240084782270768, 8240035944Yi XChen KChen JHe JDou QBai LTong HfalseIER3 drives the transition from sepsis-associated AKI to CKD by suppressing the mitochondrial translocation of PRDX5.Sepsis-associated acute kidney injury (SAKI) is a severe condition associated with high mortality and long-term complications. Currently, there is no effective strategy to halt AKI chronicization. Stress-induced senescence of renal tubular epithelial cells (RTECs) is a pivotal driving mechanism in the AKI-CKD transition. Previous scRNA-seq revealed that the expression of immediate early response gene 3 (IER3) was markedly upregulated in the senescent RTECs of patients with AKI and that the IER3⁺RTEC subpopulation exhibited diminished differentiation potential and impaired self-renewal capacity. However, the role of IER3 in RTEC stress-induced senescence following AKI remains unclear. In this study, we found that knockout of IER3 reduced mortality rates, alleviated renal injury, 2025-01-01T00:00:00Z2025 Dec2026-06-05T23:42:58.697Z2026-05-23T03:13:32.087ZS-EPMC126863284135916210.1007/s00018-025-05963-8