DUSP5 deficiency suppresses the progression of acute kidney injury by enhancing autophagy through AMPK/ULK1 pathway

Abstract

Acute kidney injury (AKI) represents a critical clinical disease characterized by the rapid decline in renal function, carrying a substantial burden of morbidity and mortality. The treatment of AKI is frequently limited by its variable clinical presentations and intricate pathophysiology, highlighting the urgent need for a deeper understanding of its pathogenesis and potential therapeutic targets. Dual-specific protein phosphatase 5 (DUSP5), a member of the serine-threonine phosphatase family, possesses the capability to dephosphorylate extracellular regulated protein kinases (ERK). DUSP5 has emerged as a pivotal player in modulating metabolic signals, inflammatory responses, and cancer progression, while also being closely associated with various kidney diseases. This study systematically scrutinized the function and mechanism of DUSP5 in AKI for the first time, unveiling a substantial increase in DUSP5 expression during AKI. Moreover, DUSP5 knockdown was observed to attenuate the production of inflammatory factors and apoptotic cells in renal tubular epithelial cells by enhancing AMPK/ULK1-mediated autophagy, thus improving renal function. In a word, DUSP5 knockdown in AKI effectively impede disease progression by activating autophagy. This finding holds promise for introducing fresh perspectives and targets for AKI treatment.