Downregulation of lncRNA TUG1 contributes to the development of sepsis-associated acute kidney injury via regulating miR-142-3p/sirtuin 1 axis and modulating NF-κB pathway.

This study intended to investigate the potential molecular mechanism of long noncoding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in the development of sepsis-associated acute kidney injury (AKI). The expression of TUG1 in the serum from patients with sepsis resulted in AKI, and healthy controls were analyzed. First, we used lipopolysaccharide (LPS; to induce AKI rat mesangial cells (RMCs) for establishing the septic AKI model in RMCs. Subsequently, TUG1 was overexpressed in RMCs and the influences of overexpression of TUG1 on cell biological processes (viability, apoptosis, and autophagy) and cytokines secretion in LPS-associated RMCs were investigated. Furthermore, the interaction between TUG1 and miR-142-3p was investigated, and the target of miR-142-3p was predicted. Also, whether TUG1 could regulate the activation of nuclear factor κB (NF-κB) signal was investigated. The results showed that TUG1 was lowly expressed in the serum patients with sepsis-associated AKI compared with that in the controls. In addition, overexpression of TUG1 relieved the injury induced by LPS in RMCs. Moreover, miR-142-3p was negatively regulated by TUG1, and TUG1 upregulation restrained LPS-associated injury by suppression of miR-142-3p. Sirtuin 1 (SIRT1) was identified as a target of miR-142-3p, which could be negatively regulated by miR-142-3p. Furthermore, overexpression of TUG1 suppressed the activation of NF-κB signal in RMCs, which was markedly reversed after miR-142-3p upregulation. Our findings reveal that downregulation of lncRNA TUG1 may promote the development and progression of sepsis-associated AKI via regulating miR-142-3p/SIRT1 axis and modulating NF-κB signal.