title: Up-Regulation of CD74 Expression in Parietal Epithelial Cells in a Mouse Model of Focal Segmental Glomerulosclerosis.
abstract: OBJECTIVE
  De novo expression of CD44 is considered as a marker of parietal epithelial cell (PEC) activation. The aim of our study was to explore CD74 expression, which can form a complex with CD44, in PECs during the progression of focal segmental glomerulosclerosis (FSGS). To clarify the role of CD74 expression and of its interaction with CD44, we generated a new mouse model with enhanced PEC activation through lipopolysaccharide (LPS) application to adriamycin (ADR)-induced nephropathy mice (LPS-treated ADR mice).
  
  
  METHODS
  As a new model, LPS was intraperitoneally injected into the mice 3 weeks after ADR injection. The mice were divided into 3 categories: control mice, ADR mice and LPS-treated ADR mice. Renal function parameters, histologic changes and immunohistochemical expression of CD74 and other PEC activation markers were analyzed after LPS application.
  
  
  RESULTS
  After LPS stimulation, the glomeruli were characterized by enlarged epithelial cells with strong CD74 expression, followed by pseudo-crescent formation. By double staining, CD74-positive enlarged cells showed co-expression of classical PEC markers, but not of Lotus tetragonolobus lectin (marker of proximal tubular cells), suggesting amplification of PEC activation. Time-course analysis displayed marked upregulation of CD74 expression during rapid PEC activation compared with CD44. Additionally, the time-dependent change in ERK phosphorylation showed a similar pattern to CD74.
  
  
  CONCLUSIONS
  Our results indicate that CD74 can be a marker for PEC activation in FSGS. By modifying the ADR mouse model through LPS treatment, we found that CD74 upregulation better reflects a rapid amplification of PEC activation than CD44 expression.
authors.affiliation: Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Okamoto
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sato
authors.forename: Asako
authors.initials: A
authors.lastname: Hayashi
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ariga
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004317:Doxorubicin / Q000633:toxicity; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015854:Up-Regulation
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D015415:Biomarkers; C476399:Cd44 protein, mouse; D000949:Histocompatibility Antigens Class II; D018960:Hyaluronan Receptors; D008070:Lipopolysaccharides; C045084:invariant chain; D004317:Doxorubicin; D048049:Extracellular Signal-Regulated MAP Kinases