title: Transforming growth factor-beta(1) and myofibroblasts: a potential pathway towards renal scarring in human glomerular disease.
abstract: OBJECTIVE
  The cellular and humoral factors involved in the development and progression of renal scarring have not been fully investigated. Transforming growth factor-beta (TGF-beta(1)) is considered to be the main fibrogenic growth factor and it is implicated in the pathogenesis of renal fibrosis in experimental and clinical nephropathies. On the other hand, collagen III is an important component of the extracellular matrix. In this study we attempted to identify any possible links between TGF-beta(1) and collagen III synthesis and expression with the expression of myofibroblasts in the evolution of renal scarring in human glomerular diseases.
  
  
  METHODS
  We studied retrospectively 40 patients with various types of primary and secondary glomerulonephritis (GN), with either proliferative or nonproliferative pattern, with emphasis on the renal synthesis of TGF-beta(1) and collagen III (detected by in situ hybridization) and their expression (detected by immunohistochemistry) as well as myofibroblast expression. The possible links of TGF-beta(1) expression with myofibroblast distribution (alpha-smooth muscle actin, alpha-SMA(+) cells) and with conventional histopathology and renal function was also examined.
  
  
  RESULTS
  TGF-beta(1) protein and mRNA were detected in the renal tubular epithelial cells and interstitium and to a lesser extent within glomeruli of patients with GN. Collagen III was mainly detected in the interstitium (peritubular and periglomerular areas) and to a lesser extent in the glomeruli. Messenger RNA for collagen III followed a similar peritubular and periglomerular distribution to that of TGF-beta(1) and alpha-SMA(+) interstitial cells. The intensity of interstitial TGF-beta(1) protein expression was significantly related to the degree of interstitial fibrosis (r = 0.628, p < 0.01), tubular atrophy (r = 0.612, p < 0.01), interstitial collagen III expression (r = 0.478, p < 0.05), and serum creatinine values (r = 0.722, p < 0.001). Also there was a close positive correlation between the severity of interstitial myofibroblast expression and interstitial TGF-beta(1) (r = 0.412, p < 0.05), as well as collagen III (r = 0.409, p < 0.05). In addition, a significant correlation was found between glomerular TGF-beta(1) expression and severity of glomerulosclerosis (r = 0.620, p < 0.01).
  
  
  CONCLUSIONS
  The results of this study suggest that TGF-beta(1) plays an important role in the pathogenesis of fibrosis developing in human kidney, during the evolution of glomerular disease. Interstitial myofibroblasts may contribute to interstitial fibrosis through the synthesis and release of both TGF-beta1 and collagen III.
authors: Department of Nephrology, University of Patras School of Medicine, Rio, Patras, Greece.
authors: D S
authors: DS
authors: Goumenos
authors: A C
authors: AC
authors: Tsamandas
authors: S
authors: S
authors: Oldroyd
authors: F
authors: F
authors: Sotsiou
authors: S
authors: S
authors: Tsakas
authors: C
authors: C
authors: Petropoulou
authors: D
authors: D
authors: Bonikos
authors: A M
authors: AM
authors: El Nahas
authors: J G
authors: JG
authors: Vlachojannis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002921:Cicatrix / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000032:analysis / Q000096:biosynthesis*; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005355:Fibrosis; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012720:Severity of Illness Index; D013223:Statistics as Topic; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1
chemical_list: D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D003094:Collagen