Lyn attenuates sepsis-associated acute kidney injury by inhibition of phospho-STAT3 and apoptosis

Sepsis-associated acute kidney injury (SA-AKI) is a life-threatening condition associated with high mortality and morbidity. However, the underlying pathogenesis of SA-AKI is still unclear. Lyn belongs to Src family kinases (SFKs), which exert numerous biological functions including modulation in receptor-mediated intracellular signaling and intercellular communication. Previous studies demonstrated that Lyn gene deletion obviously aggravates LPS-induced lung inflammation, but the role and possible mechanism of Lyn in SA-AKI have not been reported yet. Here, we found that Lyn protected against renal tubular injury in cecal ligation and puncture (CLP) induced AKI mouse model by inhibition of signal transducer and activator of transcription 3 (STAT3) phosphorylation and cell apoptosis. Moreover, Lyn agonist MLR-1023 pretreatment improved renal function, inhibited STAT3 phosphorylation and decreased cell apoptosis. Thus, Lyn appears to play a crucial role in orchestrating STAT3-mediated inflammation and cell apoptosis in SA-AKI. Hence, Lyn kinase may be a promising therapeutic target for SA-AKI.