title: Prevalence of CD44-positive glomerular parietal epithelial cells reflects podocyte injury in adriamycin nephropathy.
abstract: OBJECTIVE
  Recent study suggests that activation of parietal epithelial cells (PECs) contributes to pathogenesis of glomerulosclerosis and the activation marker CD44 increases in evolving glomerulosclerosis. Here we examined the pathogenic roles of CD44+ epithelial cells in mouse adriamycin nephropathy (ADRN), a representative rodent model for idiopathic focal segmental glomerulosclerosis (FSGS). We also evaluated whether the prevalence of CD44+ PECs reflects different levels of podocyte injuries.
  
  
  METHODS
  As a model of FSGS with different degrees of podocyte injury, ADRN models in mice of different ages were utilized. Immunohistochemistry and immunofluorescence were used to determine roles of CD44 expression.
  
  
  RESULTS
  By immunohistochemistry, CD44 expression became positive in claudin-1+ PECs and an increase in CD44+ PECs was associated with reduced expression of synaptopodin and podocin in diseased glomeruli. Furthermore, immunofluorescence staining demonstrated co-expression with osteopontin, a CD44 ligand that plays a significant role in the progression of glomerulosclerosis, thereby suggesting interactions between these molecules. Analysis of the number of WT-1+ podocytes and the levels of electron microscopic foot process effacement revealed a milder degree of podocyte injury in younger ADRN models compared to older ones. Comparative immunohistochemical analysis indicated that the prevalence of CD44+ PECs consistently reflects different degrees of podocyte injury within each different-aged ADRN model.
  
  
  CONCLUSIONS
  CD44+ PECs play significant roles in progressive glomerulosclerosis and the prevalence of the cells reflects different degrees of podocyte injury in ADRN.
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Okamoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sato
authors.forename: Hironobu
authors.initials: H
authors.lastname: Ito
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
mesh_terms: D000367:Age Factors; D000818:Animals; D002452:Cell Count; D062445:Claudin-1 / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004317:Doxorubicin / Q000009:adverse effects* / Q000494:pharmacology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D018960:Hyaluronan Receptors / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D050199:Podocytes / Q000187:drug effects / Q000473:pathology*
chemical_list: C476399:Cd44 protein, mouse; D062445:Claudin-1; D018960:Hyaluronan Receptors; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; C407223:NPHS2 protein; C503968:Synpo protein, mouse; D053495:Osteopontin; D004317:Doxorubicin