title: Apoptosis and myofibroblast expression in human glomerular disease: a possible link with transforming growth factor-beta-1.
abstract: OBJECTIVE
  The pathophysiological pathways involved in the pathogenesis and evolution of renal fibrosis, have not been fully elucidated. Transforming growth factor-beta(1) (TGF-beta(1)) is involved in the development of renal scarring. Apoptosis is responsible for intrinsic cell deletion observed in end-stage kidney disease. Myofibroblasts are involved in the development of renal fibrosis. This study investigates whether there is a potential relationship between apoptosis, myofibroblast infiltration and TGF-beta(1) expression in the kidney of patients with glomerulonephritis (GN).
  
  
  METHODS
  Forty patients with various types of GN were included in the study. Myofibroblasts and TGF-beta(1) positive cells were detected in kidney biopsies by immunohistochemistry, while apoptotic cells were detected by the in situ end labelling of fragmented DNA.
  
  
  RESULTS
  Myofibroblasts were identified in the glomeruli of some patients with severe mesangioproliferative GN and glomerulosclerosis but a more intensive myofibroblast expression was found in the renal interstitium. TGF-beta(1) was expressed in the cytoplasm of tubular epithelial cells, in the renal interstitium and in the glomeruli of patients with GN. Apoptotic cells were mainly detected in the tubules and interstitium and were present in areas with intense myofibroblast infiltration. Positive correlations were observed between the intensity of myofibroblast expression in the interstitium and apoptosis in the tubulointerstitial area (r = 0.521, p < 0.01) as well as TGF-beta(1) expression (r = 0.462, p < 0.05) and degree of renal impairment (r = 0.430, p < 0.05).
  
  
  CONCLUSIONS
  These observations suggest that myofibroblast infiltration and apoptosis along with TGF-beta(1) expression are associated with the development of interstitial fibrosis in patients with glomerular disease.
authors.affiliation: Department of Internal Medicine-Nephrology, University Hospital of Patras, GR-26500 Patras, Greece. dgoumenos@med.upatras.gr
authors.forename: Dimitrios S
authors.initials: DS
authors.lastname: Goumenos
authors.forename: Athanassios C
authors.initials: AC
authors.lastname: Tsamandas
authors.forename: A Meguid
authors.initials: AM
authors.lastname: El Nahas
authors.forename: Graham
authors.initials: G
authors.lastname: Thomas
authors.forename: Sotiris
authors.initials: S
authors.lastname: Tsakas
authors.forename: Florentia
authors.initials: F
authors.lastname: Sotsiou
authors.forename: Dionysis S
authors.initials: DS
authors.lastname: Bonikos
authors.forename: John G
authors.initials: JG
authors.lastname: Vlachojannis
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D017209:Apoptosis; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D005355:Fibrosis; D005921:Glomerulonephritis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
chemical_list: D000199:Actins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1