title: Cellular cholesterol transport proteins in diabetic nephropathy.
abstract: BACKGROUND
  Lipid accumulation has been shown to accelerate renal injury, and the intracellular accumulation of lipids may be caused by alterations in synthesis as well as lipid uptake and efflux. We have investigated the role of cellular cholesterol transport proteins including adenosine triphosphate binding cassette transporter A1 (ABCA1), G1 (ABCG1) and scavenger receptor class B type I (SR-BI) in diabetic nephropathy.
  
  
  METHODS
  Protein expression and the ability to mediate cholesterol efflux of ABCA1, ABCG1 and SR-BI was determined in human renal mesangial cells and proximal tubular epithelial cells cultured under normal or high glucose conditions. Renal expression of these cholesterol transporters was examined in a murine model of streptozotocin-induced type 1 diabetes.
  
  
  RESULTS
  ABCA1, ABCG1 and SR-BI were expressed in both human renal mesangial cells and proximal tubular epithelial cells, and mediated cholesterol efflux to apolipoprotein AI and HDL. In vitro, hyperglycemia reduced the expression and the ability to mediate cholesterol efflux of all three cholesterol transporters (p<0.05). In vivo studies showed that intra-renal accumulation of lipids was increased in diabetic mice, particularly in mice with nephropathy. This was associated with a significant reduction in the expression of ABCA1, ABCG1 and SR-BI in the kidneys. These changes were already seen in diabetic mice without nephropathy and preceded the development of nephropathy. Diabetic mice with nephropathy had the lowest level of these cholesterol transporters.
  
  
  CONCLUSIONS
  Inducing diabetes with streptozotocin significantly reduced renal expression of ABCA1, ABCG1 and SR-BI. Defects in cholesterol export pathway in renal cells could therefore promote cholesterol accumulation and might contribute to the development of diabetic nephropathy.
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Joseph G S
authors.initials: JG
authors.lastname: Tsun
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Susan
authors.initials: S
authors.lastname: Yung
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Mel K M
authors.initials: MK
authors.lastname: Chau
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Sammy W M
authors.initials: SW
authors.lastname: Shiu
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Tak Mao
authors.initials: TM
authors.lastname: Chan
authors.affiliation: Department of Medicine, University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Kathryn C B
authors.initials: KC
authors.lastname: Tan
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000097:blood / Q000401:mortality*; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000097:blood; D008297:Male; D008811:Mice, Inbred DBA; D051122:Scavenger Receptors, Class B / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D008055:Lipids; D051122:Scavenger Receptors, Class B; D002784:Cholesterol