title: Vitamin D-binding protein is required for the protective effects of vitamin D in renal fibroblasts and is phosphorylated in diabetic rats.
abstract: Serum vitamin D is bound to vitamin D-binding protein (DBP). We studied the roles of DBP in streptozotocin-diabetic rats and high glucose (HG)-cultured cells. In diabetic rat sera, there was one upregulated (with a lower isoelectric point [pI], phosphorylated at S268, S270, S464 and T269) and one downregulated (with a higher pI, phosphorylated at S454 and S457) DBP. DBP levels with lower pI were increased in diabetic rat kidney and liver. HG (30 mM) increased DBP protein expression in NRK-49F cells and Clone-9 hepatocytes. HG decreased pI of DBP in Clone-9 hepatocytes. Moreover, DBP short hairpin ribonucleic acid attenuated 1,25-(OH)2D3-induced attenuation of HG-induced renin (but not collagen IV and fibronectin) protein expression in NRK-49F cells. Thus, DBP level is increased whereas DBP is phosphorylated in diabetic rat serum. HG increased DBP protein expression in renal fibroblasts and hepatocytes. Moreover, DBP is required for vitamin D-induced attenuation of HG-induced renin in NRK-49F cells.
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan.
authors.forename: Chi-Hsien
authors.initials: CH
authors.lastname: Chou
authors.affiliation: Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Taiwan. Electronic address: layech@kmu.edu.tw.
authors.forename: Lea-Yea
authors.initials: LY
authors.lastname: Chuang
authors.affiliation: Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Taiwan.
authors.forename: Chi-Yu
authors.initials: CY
authors.lastname: Lu
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan. Electronic address: guhjy@kmu.edu.tw.
authors.forename: Jinn-Yuh
authors.initials: JY
authors.lastname: Guh
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D013552:Swine; D015854:Up-Regulation; D014807:Vitamin D / Q000378:metabolism*; D014809:Vitamin D-Binding Protein / Q000378:metabolism*
chemical_list: D014809:Vitamin D-Binding Protein; D014807:Vitamin D; D005947:Glucose
keywords: Diabetic nephropathy; High glucose; NRK-49F cells; Phosphorylation; Vitamin D-binding protein