Curcumin reduces LPS-induced septic acute kidney injury through suppression of lncRNA PVT1 in mice

Abstract

ObjectiveTo investigate the protective effects of curcumin on LPS-induced septic acute kidney injury and to explore its underlying molecular mechanisms. MethodsA mouse model of septic acute kidney injury (AKI) was given an intraperitoneal injection of lipopolysaccharide (LPS), followed by administration of variable levels of curcumin (intragastric). And NRK cells were used as the kidney cell model for all in vitro studies. ResultsCurcumin significantly decreased the levels of serum Scr, BUN, and Cyc c and reduced kidney injury in LPS-induced AKI mice. Kidney tissues of LPS-induced AKI mice showed an increase in PVT1, ED-1, TNF-α, IL-1β, IL-6, p-IkBα/IkBα, p-p65/p65, p-JNK/JNK, and p-c-JUN/c-JUN expression levels; however, treatment with curcumin significantly reduced this effect. Curcumin increased the survival rate NRK cells exposed to LPS-induced inflammation in vitro. Moreover, NRK cells that overexpressed PVT1 had lower survival rates than WT NRK cells obtained from mice that received curcumin treatment after treating with LPS. Additionally, curcumin reduced the LPS-induced increase in Bax, cleaved-caspase3/caspase 3, p-IkBα/IkBα, p-p65/p65, p-JNK/JNK, and p-c-JUN/c-JUN protein expression, and increased Bcl2 protein expression in NRK cells. However, the extent of these changes was low in NRK cells that overexpressed PVT1. ConclusionCurcumin decreased PVT1 expression in LPS-induced septic acute kidney tissues and reduced LPS-induced septic acute kidney injury in mice. This might be related to the inhibition of the JNK/NF-κB pathway by curcumin through suppression of lncRNA PVT1.