title: Vitamin D and its receptor regulate lipopolysaccharide-induced transforming growth factor-β, angiotensinogen expression and podocytes apoptosis through the nuclear factor-κB pathway.
abstract: OBJECTIVE
  To investigate the effects of vitamin D and its receptor on cytokines expression and podocytes apoptosis.
  
  
  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-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.
  
  
  CONCLUSIONS
  Vitamin 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.
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Pengyuan
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Haipeng
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yanbing
authors.initials: Y
authors.lastname: Li
mesh_terms: D000808:Angiotensinogen / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008070:Lipopolysaccharides; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014807:Vitamin D / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D018167:Receptors, Calcitriol; D016212:Transforming Growth Factor beta; D000808:Angiotensinogen; D014807:Vitamin D
keywords: Nephropathy; Podocyte; Vitamin D