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

作者：Xu, Lijuan; Zhang, Pengyuan; Guan, Hongyu; Huang, Zhimin; He, Xiaoying; Wan, Xuesi; Xiao, Haipeng; Li, Yanbing^*

来源：Journal of Diabetes Investigation, 2016, 7(5): 680-688.

DOI：10.1111/jdi.12505

• Nephropathy
• Podocyte
• Vitamin D

Aims/Introduction: To investigate the effects of vitamin D and its receptor on cytokines expression and podocytes apoptosis. @@@ Materials and Methods: Cultured 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. @@@ Results: In a lipopolysaccharide-induced state, expressions of transforming growth factor-beta, angiotensinogen and vascular endothelial growth factor were similarly increased. Transforming growth factor-beta 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-kappa B and the inhibitor kinase proteins. After siRNA transfection, those proteins levels were further elevated. The originally increased transforming growth factor-beta 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-kappa B 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. @@@ Conclusions: Vitamin D and its receptor might be involved in the progression of diabetic nephropathy by regulating transforming growth factor-beta, angiotensinogen expression and apoptosis of podocytes. The processes are mediated through the signaling of nuclear factor-kappa B pathway.

• 出版日期2016-9
• 单位中山大学