title: Histological changes and immunohistochemical markers in the assessment of glomerulosclerosis in patients with glomerulonephritis.
abstract: BACKGROUND
  Glomerular cells (mesangial, endothelial, epithelial) are activated during glomerulonephritis, a process indicated by the expression of the immunohistochemical marker α-smooth muscle actin (SMA). Many growth factors participate in the above-mentioned processes, among them of great importance is the transforming growth factor β (TGF-β). The result of these changes is represented by active lesions (mesangial matrix increase, mesangial cell proliferation) and chronic fibrotic lesions (glomerulosclerosis).
  
  
  METHODS
  We studied a group of 41 patients with primary and secondary glomerulonephritis (24 males, 17 females, mean age 45.5 ± 12.9 years), which underwent kidney biopsies, processed in light microscopy. We performed immunohistochemistry procedures with monoclonal antibodies (performed with the LSAB2-HRP system: anti-α-SMA, and anti-TGF-β), which were assessed using a semiquantitative score, that was correlated with the histological and biological data. In order to quantify the histological changes and to assess the extent of active-inflammatory and chronic-sclerotic/fibrotic lesions, we adapted a scoring system initially used only for lupus nephritis, and ANCA-associated vasculitis.
  
  
  RESULTS
  TGF-β expression in glomerular endothelial cells correlated with mesangial matrix increase (r=0.28, p<0.05), total activity index (r=0.29, p<0.05) and total chronicity index (r=0.34, p<0.05). Glomerular epithelial cell TGF-β correlates with mesangial proliferation (r=0.29, p<0.05), mesangial matrix increase (r=0.4, p<0.01) and total activity index (r=0.28, p<0.05). We observed a strong correlation between endothelial immunolabeling of SMA and the mesangial proliferation score (r=-0.96, p<0.005) and also an indirect correlation with the glomerulosclerosis score (r=-0.35, p<0.05) and the total chronicity index (r=-0.39, p<0.05). Concerning biological data there was a correlation between mesangial SMA expression and serum creatinine (r=0.60, p<0.001) and an indirect correlation with GFR (r=-0.37, p<0.05).
  
  
  CONCLUSIONS
  We conclude that TGF-β has a key role in determining glomerulosclerosis especially through mesangial matrix increase, but possibly also through mesangial cells proliferation. Another role of this growth factor is related to transdifferentiation, not only epithelial-mesenchymal, but also endothelial-mesenchymal.
authors: Department of Nephrology, Victor Babeş University of Medicine and Pharmacy, Timisoara, Romania. flaviu_bob@yahoo.com
authors: F R
authors: FR
authors: Bob
authors: Gh
authors: G
authors: Gluhovschi
authors: Diana
authors: D
authors: Herman
authors: Gh
authors: G
authors: Bozdog
authors: Cristina
authors: C
authors: Gluhovschi
authors: Silvia
authors: S
authors: Velciov
authors: Elena
authors: E
authors: Potencz
authors: Ligia
authors: L
authors: Petrica
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D005920:Glomerular Mesangium / Q000378:metabolism / Q000473:pathology; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012598:Sclerosis; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016212:Transforming Growth Factor beta