title: Localization of SPARC in developing, mature, and chronically injured human allograft kidneys.
abstract: BACKGROUND
  The matricellular protein SPARC (secreted protein acidic and rich in cysteine) is expressed during development, tissue remodeling and repair. It functions as an endogenous inhibitor of cell proliferation, regulates angiogenesis, regulates cell adhesion to extracellular matrix, binds cytokines such as platelet derived growth factor and stimulates transforming growth factor-beta (TGF-beta) production. This study describes the expression of SPARC during human renal development, in normal kidneys and during renal allograft rejection.
  
  
  METHODS
  A total of 60 renal specimens, including normal areas from tumor nephrectomies (N = 24), fetal kidneys (N = 27) and explanted renal allografts (N = 9), were included in the study. SPARC protein was localized by immunohistochemistry using two different antibodies. On consecutive sections SPARC mRNA was detected by in situ hybridization.
  
  
  RESULTS
  In the normal adult kidney SPARC protein was expressed by visceral and parietal epithelial cells, collecting duct epithelium (CD), urothelium, smooth muscle cells of muscular arteries and focally in interstitial cells. During renal development immature glomeruli demonstrated a polarized SPARC expression in visceral epithelial cells at their surface abutting the capillary basement membranes. In the fully differentiated glomeruli the expression pattern mirrored that of the adult kidney. Furthermore, SPARC was abundantly expressed by derivatives of the ureteric bud, and smooth muscle cells of arterial walls. During chronic allograft rejection SPARC is expressed in neointimal arterial smooth muscle cells, infiltrating inflammatory cells as well as by interstitial myofibroblasts in areas of interstitial fibrosis. SPARC mRNA synthesis detected by in situ hybridization mirrored these protein expression patterns.
  
  
  CONCLUSIONS
  These studies co-localize SPARC to several sites of renal injury previously shown to be sites of PDGF B-chain expression and/or activity. We speculate that SPARC could function as an accessory molecule in chronic PDGF-mediated sclerosing interstitial and vascular injury. SPARC localization to glomerular epithelial cells corresponds to similar findings in rodents, and may reflect its role in cell adhesion and /or regulation of cell shape.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle Washington, USA. calp@u.washington.edu
authors.forename: Charles E
authors.initials: CE
authors.lastname: Alpers
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Hudkins
authors.forename: Stephan
authors.initials: S
authors.lastname: Segerer
authors.forename: E Helene
authors.initials: EH
authors.lastname: Sage
authors.forename: Raimund
authors.initials: R
authors.lastname: Pichler
authors.forename: William G
authors.initials: WG
authors.lastname: Couser
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: James A
authors.initials: JA
authors.lastname: Bassuk
mesh_terms: D000328:Adult; D000918:Antibody Specificity; D002908:Chronic Disease; D005333:Fetus / Q000737:chemistry; D005347:Fibroblasts / Q000737:chemistry; D005355:Fibrosis; D006084:Graft Rejection / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000737:chemistry* / Q000196:embryology* / Q000601:surgery; D016030:Kidney Transplantation; D032389:Myocytes, Smooth Muscle / Q000737:chemistry; D015676:Osteonectin / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D014184:Transplantation, Homologous
chemical_list: D015676:Osteonectin; D012333:RNA, Messenger