title: Modulation of nephrin in the diabetic kidney: association with systemic hypertension and increasing albuminuria.
abstract: OBJECTIVE
  Nephrin, a cytoskeletal protein which localizes to the slit pore of podocytes, may play a role in proteinuria. This study examines the possible relationship between nephrin expression and albuminuria in normotensive and hypertensive diabetic rats.
  
  
  METHODS
  Streptozotocin diabetes was induced in both Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Diabetic and control animals were sacrificed and the kidneys obtained after 8, 16 and 24 weeks. The glomerular filtration rate (GFR) and albuminuria were also measured. Glycaemic control was assessed by measurement of plasma glucose and glycated haemoglobin (HbA1c). Nephrin gene expression was quantitated by real-time polymerase chain reaction (PCR) and localized by in situ hybridization. Nephrin protein expression was localized by immunohistochemistry and quantitated.
  
  
  RESULTS
  Following a transient rise at 8 weeks in the diabetic SHR (P < 0.05 versus control SHRs), nephrin gene expression, as determined by real-time PCR, was significantly decreased at 16 and 24 weeks (P < 0.05 versus control SHRs). In situ hybridization confirmed similar changes in nephrin gene expression, which were confined to the glomeruli. This reduction in glomerular nephrin gene expression was associated with increasing albuminuria at 16 and 24 weeks in diabetic SHRs. There were no significant changes in nephrin gene expression, either by real-time reverse transcription polymerase chain reaction or in situ hybridization, observed in normotensive diabetic WKY rats, in the context of much less albuminuria in this group. Immunohistochemistry for nephrin protein revealed a greater depletion in renal nephrin content in SHR than in WKY rats after 24 weeks of diabetes.
  
  
  CONCLUSIONS
  Reduction in renal nephrin gene and protein expression is closely associated with the development of albuminuria, as observed in an experimental model of diabetes and hypertension.
authors: Department of Medicine and Endocrinology, University of Melbourne, Austin, Australia. jforbes@austin.unimelb.edu.au
authors: Josephine M
authors: JM
authors: Forbes
authors: Fabrice
authors: F
authors: Bonnet
authors: Leileata M
authors: LM
authors: Russo
authors: Wendy C
authors: WC
authors: Burns
authors: Zemin
authors: Z
authors: Cao
authors: Riccardo
authors: R
authors: Candido
authors: Hiroshi
authors: H
authors: Kawachi
authors: Terri J
authors: TJ
authors: Allen
authors: Mark E
authors: ME
authors: Cooper
authors: George
authors: G
authors: Jerums
authors: Tanya M
authors: TM
authors: Osicka
mesh_terms: D000419:Albuminuria / Q000209:etiology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000150:complications* / Q000378:metabolism* / Q000652:urine; D006973:Hypertension / Q000378:metabolism* / Q000652:urine; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014018:Tissue Distribution
chemical_list: D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; C113267:nephrin