SB-525334 ameliorates renal injury in diabetic kidney disease mouse model via suppressing inflammation

Abstract

BackgroundDiabetic kidney disease (DKD; also known as diabetic nephropathy) is a typical complication of diabetes mellitus characterised by renal injury due to disturbances in glucose metabolism, in which renal tubular damage caused by chronic inflammation has been shown to be closely associated with the development of end-stage renal disease (ESRD). However, there are insufficient effective therapeutic agents to halt the progression of DKD. MethodsIn the present study, we screened differential gene expression profiles associated with DKD by mining the GEO database through differential and enrichment analyses. Furthermore, systemic in vivo and in vitro experiments were designed to explore the mechanism through which the potential therapeutic agent SB-525334 improves DKD. ResultsSB-525334 ameliorated DKD-induced kidney injury by regulating inflammatory cytokines (TGF-β1, IL-6, IL-10) as well as promoting the translation of M1 (iNOS) macrophage to M2 (CD206) macrophage. In addition, SB-525334 ameliorates kidney injury caused by DKD through inhibiting inflammation through regulating the expression of key proteins in the TGF-β1 /JNK and TGF-β1 /Smad signaling pathways. For studies in vitro, inflammation induced by LPS in vitro was inhibited significantly after the administration of SB-525334 through down-regulating pro-inflammatory cytokines, promoting macrophage conversion from M1 to M2, and inhibiting the activation of TGF-β1 /JNK and TGF-β1 /Smad pathways. ConclusionsThese results highlight that the target compound SB-525334 could serve as a novel potential therapeutic agent and ameliorate DKD in an inflammation-inhibiting manner.