Rab27a Deficiency Mitigates Mitochondrial Damage by Upregulating PPAR-γ in Sepsis Associated Acute Kidney Injury

Sepsis-associated acute kidney injury (SA-AKI) is a significant form of organ dysfunction that affects a substantial proportion of patients with sepsis, contributing to increased mortality. However, the potential mechanisms underlying SA-AKI remain poorly understood. In this study, we identified Rab27a as a critical factor in regulating SA-AKI, with its upregulated expression both in vitro and in vivo. The silence of Rab27a mitigated LPS-induced injury and mitochondrial dysfunction in HK-2 cells, leading to enhanced cell migration and functional improvement. Notably, the protective effects of Rab27a knockdown were reversed upon silencing PPAR-γ, highlighting a potential correlation between these proteins. Furthermore, a significant interaction between PPAR-γ and AMPK-α1 was observed following Rab27a knockdown in RTECs during SA-AKI. In conclusion, we demonstrated that Rab27a served as a key mediator in the pathogenesis of SA-AKI, influencing RTEC function and mitochondrial integrity.