title: Differential expression of nephrin in acquired human proteinuric diseases.
abstract: BACKGROUND
  The slit-diaphragm protein nephrin is an essential component of the glomerular filtration barrier. It is not clear whether renal injury in patients with acquired proteinuric diseases is associated with altered regulation of the nephrin gene or protein.
  
  
  METHODS
  We examined expression patterns of nephrin protein and messenger RNA (mRNA) in renal biopsy specimens from patients with minimal lesion (n = 7), focal segmental glomerulosclerosis (FSGS; n = 14), or membranous nephropathy (MN; n = 7) and controls (n = 8) by immunohistochemistry, immunoelectron microscopy, in situ hybridization, and polymerase chain reaction (PCR) amplification of nephrin complementary DNA.
  
  
  RESULTS
  In normal kidney, nephrin staining showed a diffuse interrupted linear pattern along the glomerular basement membrane (GBM). Nephrin staining in minimal lesion specimens showed a finely granular pattern along the GBM and was positive in cell bodies of visceral glomerular epithelial cells. Nephrin staining was most disrupted in FSGS specimens. Immunoelectron microscopy showed that nephrin-specific gold particles were almost absent in effaced foot processes in proteinuric patients. An in situ hybridization study showed significantly decreased nephrin mRNA-expressing cells in cases of FSGS and MN compared with controls. Reverse-transcription PCR showed significantly lower levels of nephrin mRNA in cases of FSGS and MN than controls, but no significant difference between minimal lesion cases and controls. Relative levels of glomerular nephrin mRNA correlated inversely with percentage of glomeruli with sclerosis in proteinuric diseases.
  
  
  CONCLUSIONS
  These results suggest that nephrin-expression patterns in proteinuric diseases are different according to the specific glomerular disease or severity of glomerular damage.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Byoung Kwon
authors.initials: BK
authors.lastname: Kim
authors.forename: Hye Kyoung
authors.initials: HK
authors.lastname: Hong
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Hyun Soon
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000737:chemistry / Q000293:injuries / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics* / Q000276:immunology; D011507:Proteinuria / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D008565:Membrane Proteins; D011506:Proteins; D012333:RNA, Messenger; C113267:nephrin