title: Fli-1 transcription factor affects glomerulonephritis development by regulating expression of monocyte chemoattractant protein-1 in endothelial cells in the kidney.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Rheumatology & Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Eiji
authors.initials: E
authors.lastname: Suzuki
authors.forename: Eva
authors.initials: E
authors.lastname: Karam
authors.forename: Sarah
authors.initials: S
authors.lastname: Williams
authors.forename: Dennis K
authors.initials: DK
authors.lastname: Watson
authors.forename: Gary
authors.initials: G
authors.lastname: Gilkeson
authors.forename: Xian K
authors.initials: XK
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D015870:Gene Expression; D005921:Glomerulonephritis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008181:Lupus Nephritis / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D051789:Proto-Oncogene Protein c-fli-1 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C497426:Fli1 protein, mouse; D051789:Proto-Oncogene Protein c-fli-1; D034741:RNA, Small Interfering; D004247:DNA