Background: The pathogenesis of acute kidney injury (AKI) is not fully understood. Tax1-binding protein 1 (TAX1BP1) modulates inflammation and apoptosis through the NF-kB signaling pathway, however, its specific role in ischemic AKI remains unclear.
Methods: We injected a TAX1BP1 overexpression plasmid into the tail vein of male C57BL/6 mice, followed by clamping the bilateral renal arteries to induce AKI. Additionally, TAX1BP1 overexpression and silencing vectors were transfected into NRK52E cells to establish an in vitro hypoxia-reoxygenation model. Renal tubular necrosis was assessed using PAS and H&E staining. Expression levels of TAX1BP1, caspase-3, Bcl2, phosphorylated p65, and total p65 were measured through Western blot in both models. RT-PCR was used to evaluate KIM-1, NGAL, IL-6, and TNFα expression, while TUNEL staining detected apoptosis in renal tubular epithelial cells. RNA sequencing identified potential TAX1BP1 targets, which were validated via Western blot and RT-PCR.
Results: Our results indicate that TAX1BP1 significantly influences ischemic AKI by modulating apoptosis and inflammation in kidney tissues. In vitro studies confirmed its critical role in renal tubular epithelial cell apoptosis and inflammation through NF-kB activation, potentially via PMAIP1.
Conclusion: TAX1BP1 may protect renal tubular epithelial cells by targeting PMAIP1 through the NF-kB signaling pathway in ischemic AKI.
Keywords: AKI; Apoptosis; Ischemia–reperfusion; NF-kB; PMAIP1; TAX1BP1.
© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.