Vitamin D and its receptor regulate lipopolysaccharide-induced transforming growth factor-β, angiotensinogen expression and podocytes apoptosis through the nuclear factor-κB pathway.

Abstract

Aims/IntroductionTo investigate the effects of vitamin D and its receptor on cytokines expression and podocytes apoptosis.Materials and MethodsCultured mouse podocytes were pre‐incubated with vitamin D or transiently transfected with small interfering ribonucleic acid (RNA) to knock down the vitamin D receptor. Lipopolysaccharide was used to mimic the inflammation status of diabetes.ResultsIn a lipopolysaccharide‐induced state, expressions of transforming growth factor‐β, angiotensinogen and vascular endothelial growth factor were similarly increased. Transforming growth factor‐β and angiotensinogen levels originally elevated by lipopolysaccharide challenge were distinctly reduced after pre‐incubation with vitamin D. Whereas after vitamin D receptor small interfering (si)RNA transfection, the aforementioned cytokines had opposite changes as expected. However, neither vitamin D pretreatment nor vitamin D receptor siRNA transfection influenced the previously increased vascular endothelial growth factor expression at messenger RNA or protein levels. When pretreated with vitamin D, decreases were observed for phosphorylated inhibitor‐κB and the inhibitor kinase proteins. After siRNA transfection, those proteins levels were further elevated. The originally increased transforming growth factor‐β and angiotensinogen levels as a result of lipopolysaccharide stimulation were reduced at both the messenger RNA and protein levels after the specific inhibition of the nuclear factor‐κB pathway with pyrrolidine dithiocarbamate. The apoptosis rate of podocytes was decreased in a parallel manner after vitamin D pre‐incubation, and increased after siRNA transfection, which was also suppressed by pyrrolidine dithiocarbamate.ConclusionsVitamin D and its receptor might be involved in the progression of diabetic nephropathy by regulating transforming growth factor‐β, angiotensinogen expression and apoptosis of podocytes. The processes are mediated through the signaling of nuclear factor‐κB pathway.