Thymosin β4 alleviates sepsis-associated acute kidney injury by suppressing MAPK signaling pathway

Sepsis-associated acute kidney injury (SA-AKI) is a common complication in septic patients and is associated with high mortality and progression to chronic kidney disease (CKD). Previous studies have demonstrated that thymosin β4 (Tβ4) attenuates lipopolysaccharide (LPS)-induced liver injury and ischemic AKI via inhibiting inflammatory response. Here, we aimed to investigate the effects of Tβ4 on SA-AKI and elucidate its underlying mechanisms. In vivo and in vitro models of SA-AKI were established using LPS. Tβ4 was administered 30 min after LPS exposure. Transcriptome sequencing was performed to explore the underlying molecular mechanisms, which were further validated by western blotting in vitro. In SA-AKI mice, serum Tβ4 levels were markedly decreased. Administering Tβ4 significantly ameliorated the renal dysfunction and morphological injury in LPS-treated mice. Consistently, Tβ4 reduced renal inflammation and apoptosis in SA-AKI mice. Transcriptome-sequencing analysis indicated that MAPK signaling pathway was involved in both SA-AKI pathogenesis and the protective effect of Tβ4. Western blotting of the renal tissues confirmed that LPS markedly increased the phosphorylation of JNK1/2, p38 MAPK and ERK1/2, whereas Tβ4 significantly suppressed their activation. Furthermore, pharmacological activation of MAPK pathway with anisomycin abrogated the inhibitory effects of Tβ4 on MAPK signaling in in vitro SA-AKI models. In conclusion, Tβ4 alleviates renal inflammation and apoptosis in SA-AKI by suppressing MAPK signaling pathway. Tβ4 may represent a potential therapeutic strategy for early intervention in SA-AKI.