title: Protective effect of statin therapy on connective tissue growth factor induction by diabetes in vivo and high glucose in vitro.
abstract: Transcriptional activity of connective tissue growth factor (CTGF) promoter in transfected HEK293 cells was determined by luciferase assays. Secreted CTGF in cultured human mesangial cells was measured by enzyme-linked immunosorbent assay (ELISA). CTGF in urine and plasma was also measured in 405 subjects with/without type 2 diabetes. Our results showed that high glucose significantly increased transcription of the promoter in the transfected cells by more than 2.5-folds (p < 0.0005). CTGF secretion was induced by high glucose in the cells (p < 0.0005). These increases were inhibited by simvastatin. Urine CTGF was positively associated with plasma CTGF in both type 2 diabetes (p = 0.0005) and controls (p = 0.01). Urine CTGF levels in patients with macroalbuminuria were significantly higher than patients without macroalbuminuria (p < 0.05). In conclusion, our in vitro study suggests that statin may have a renal-protective effect through the inhibition of CTGF expression. Urine CTGF may be a good marker for the prediction of diabetic nephropathy.
authors.affiliation: Molecular Medicine, Institute of Translational & Stratified Medicine, Plymouth University Schools of Medicine & Dentistry , United Kingdom.
authors.forename: Bingmei
authors.initials: B
authors.lastname: Yang
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Hodgkinson
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Shaw
authors.forename: Beverley A
authors.initials: BA
authors.lastname: Millward
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Demaine
mesh_terms: D000419:Albuminuria / Q000652:urine; D015415:Biomarkers / Q000652:urine; D002461:Cell Line, Transformed; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis* / Q000235:genetics / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000652:urine; D005786:Gene Expression Regulation / Q000187:drug effects; D005920:Glomerular Mesangium / Q000737:chemistry / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D049410:Luciferases, Renilla / Q000235:genetics; D011401:Promoter Regions, Genetic; D019821:Simvastatin / Q000008:administration & dosage / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
chemical_list: D015415:Biomarkers; D055513:Connective Tissue Growth Factor; D019821:Simvastatin; D049410:Luciferases, Renilla; D005947:Glucose