title: [Role of nuclear factor of activated T-cells cytoplasmic 1 on vascular calcification in rats with chronic renal failure].
abstract: Objective:To explore the role of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) on vascular calcification in chronic renal failure rats.Methods:Nineteen male Sprague-Dawley (SD) rats were randomly divided into three groups: sham-operated group (n=6), 5/6 Nephrectomy (Nx) group (n=6), 5/6 Nx+ calcitriol group (n=7). Vascular calcification was determined by von Kossa staining and orthocresolphthalein complexone (OCPC) method. Protein expressions of NFATc1 and runt-related transcription factor 2 (Runx2) in aortas were measured by immunohistochemistry.In vitro,vascular smooth muscle cells (VSMCs) were primarily cultured and calcification was induced by β-glycerophosphate (β-GP). These cells were then randomly divided into control group, calcification group (10 mmol/L β-GP) and cyclosporin A (CsA) intervention group (10 mmol/L β-GP+ 1 μg/ml CsA). Calcium deposition was measured by Alizarin red staining and OCPC method; alkaline phosphatase (ALP) activity was measured by enzyme-linked immunosorbent assay. RT-PCR and Western blotting were used to observe the mRNA and protein expression of VSMCs NFATc1 and Runx2 respectively.Results:Compared to that in sham-operated and 5/6 Nx group, the expression of NFATc1 was obviously up-regulated in 5/6 Nx+ calcitriol group (7.20±0.46 vs 1.52±0.77, 2.04±1.31,P<0.05).In vitro,VSMCs calcification was successfully induced by high phosphorus environment, and RT-PCR and Western blotting showed that the expressions of NFATc1 and Runx2 were up-regulated (P<0.05). The calcification level in CsA intervention group was lower than that in calcification group [(60.86±7.95) vs (107.20±11.07) mg/g,P<0.05], and expression of Runx2 (mRNA and protein level) and ALP activity [(48.63±3.02) vs (98.75±3.46) U/g,P<0.05] decreased as well.Conclusion:NFATc1 contributes to accelerating vascular calcification in rat with chronic renal failure, the possible mechanism of which is that NFATc1 promotes VSMCs transformation to osteogenic phenotype.
authors.affiliation: Department of Nephrology, the Forth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
authors.forename: J X
authors.initials: JX
authors.lastname: Zhang
authors.forename: J S
authors.initials: JS
authors.lastname: Xu
authors.forename: Y Y
authors.initials: YY
authors.lastname: Han
authors.forename: Y L
authors.initials: YL
authors.lastname: Bai
authors.forename: L W
authors.initials: LW
authors.lastname: Cui
authors.forename: H R
authors.initials: HR
authors.lastname: Zhang
authors.forename: S L
authors.initials: SL
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001011:Aorta; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit; D003593:Cytoplasm; D005994:Glycerophosphates; D007676:Kidney Failure, Chronic; D008297:Male; D009131:Muscle, Smooth, Vascular; D032389:Myocytes, Smooth Muscle; D010012:Osteogenesis; D010758:Phosphorus; D051381:Rats; D017207:Rats, Sprague-Dawley; D013601:T-Lymphocytes; D015854:Up-Regulation; D061205:Vascular Calcification
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D005994:Glycerophosphates; D010758:Phosphorus; C031463:beta-glycerophosphoric acid
keywords: Calcinosis; Core binding factor alpha 1 subunit; Kidney failure, chronic; Muscle, smooth, vascular; NFATC transcription factors