Fli-1 transcription factor affects glomerulonephritis development by regulating expression of monocyte chemoattractant protein-1 in endothelial cells in the kidney

Clin Immunol. 2012 Dec;145(3):201-8. doi: 10.1016/j.clim.2012.09.006. Epub 2012 Sep 28.


Expression of transcription factor Fli-1 is implicated in the development of glomerulonephritis. Fli-1 heterozygous knockout (Fli1(+/-)) NZM2410 mice, a murine model of lupus, had significantly improved survival and reduced glomerulonephritis. In this study, we found that infiltrated inflammatory cells were significantly decreased in the kidneys from Fli-1(+/-) NZM2410 mice. The expression of monocyte chemoattractant protein-1 (MCP-1) was significantly decreased in kidneys from Fli-1(+/-) NZM2410 mice. The primary endothelial cells isolated from the kidneys of Fli-1(+/-) NZM2410 mice produced significantly less MCP-1. In endothelial cells transfected with specific Fli-1 siRNA the production of MCP-1 was significantly reduced compared to cells transfected with negative control siRNA. By Chromatin Immunoprecipitation (ChIP) assay, we further demonstrated that Fli-1 directly binds to the promoter of the MCP-1 gene. Our data indicate that Fli-1 impacts glomerulonephritis development by regulating expression of inflammatory chemokine MCP-1 and inflammatory cell infiltration in the kidneys in the NZM2410 mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites / genetics
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • DNA / genetics
  • DNA / metabolism
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Gene Expression
  • Glomerulonephritis / etiology*
  • Glomerulonephritis / genetics
  • Glomerulonephritis / metabolism*
  • Glomerulonephritis / pathology
  • Heterozygote
  • Humans
  • Kidney / metabolism
  • Kidney / pathology
  • Lupus Nephritis / etiology
  • Lupus Nephritis / genetics
  • Lupus Nephritis / metabolism
  • Lupus Nephritis / pathology
  • Mice
  • Mice, Knockout
  • Promoter Regions, Genetic
  • Proto-Oncogene Protein c-fli-1 / antagonists & inhibitors
  • Proto-Oncogene Protein c-fli-1 / deficiency
  • Proto-Oncogene Protein c-fli-1 / genetics
  • Proto-Oncogene Protein c-fli-1 / metabolism*
  • RNA, Small Interfering / genetics


  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Fli1 protein, mouse
  • Proto-Oncogene Protein c-fli-1
  • RNA, Small Interfering
  • DNA