title: Transforming growth factor-beta(1) in the kidney and urine of patients with glomerular disease and proteinuria.
abstract: BACKGROUND
  Transforming growth factor-beta(1) (TGF-beta(1)) is the major fibrogenic growth factor implicated in the pathogenesis of renal scarring. Proteinuria is a poor prognostic feature for various types of glomerular disease and its toxic action may be related to the activation of tubular epithelial cells towards increased production of cytokines and chemoattractant peptides. In this work we studied the site of synthesis and expression profile of TGF-beta(1) in the renal tissue of patients with heavy proteinuria and examined the relation of this expression with the urinary excretion of TGF-beta(1).
  
  
  METHODS
  Twenty-five patients with heavy proteinuria (8.4+/-3.0 g/24 h) were included in the study. All patients underwent a diagnostic kidney biopsy and were commenced on immunosuppressive therapy with corticosteroids and cyclosporin. The sites of synthesis and expression profile of TGF-beta(1) mRNA and protein in the kidney were examined by in situ hybridization and immunohistochemistry. Urinary and plasma TGF-beta(1) levels were determined by ELISA before the initiation of treatment and 6 months later and compared with those of normal subjects and of patients with IgA nephropathy and normal urinary protein excretion.
  
  
  RESULTS
  The site of synthesis and expression of TGF-beta(1) in the renal tissue of patients with heavy proteinuria was mainly localized within the cytoplasm of tubular epithelial cells. Interstitial expression was also present but glomerular TGF-beta(1) expression was found only in patients with mesangial proliferation. Urinary TGF-beta(1) excretion was significantly higher in nephrotic patients compared with normal subjects and with patients with IgA nephropathy and normal urinary protein excretion (783+/-280 vs 310+/-140 and 375+/-90 ng/24 h, respectively; P<0.01). In patients with remission of proteinuria after immunosuppressive therapy, urinary TGF-beta(1) excretion was significantly reduced (from 749+/-290 to 495+/-130 ng/24 h; P<0.01), while in patients with persistent nephrotic syndrome, it remained elevated.
  
  
  CONCLUSIONS
  The localization of TGF-beta(1) mRNA and protein within tubular epithelial cells, along with its increased urinary excretion in patients with nephrotic syndrome, suggest the activation of these cells by filtered protein towards increased TGF-beta(1) production.
authors.affiliation: Department of Internal Medicine-Nephrology, University Hospital, Patras, Greece. dgoumenos@med.upatras.gr
authors.forename: Dimitrios S
authors.initials: DS
authors.lastname: Goumenos
authors.forename: Sotiris
authors.initials: S
authors.lastname: Tsakas
authors.forename: Abdel Meguid
authors.initials: AM
authors.lastname: El Nahas
authors.forename: Sotiria
authors.initials: S
authors.lastname: Alexandri
authors.forename: Simon
authors.initials: S
authors.lastname: Oldroyd
authors.forename: Pantelitsa
authors.initials: P
authors.lastname: Kalliakmani
authors.forename: John G
authors.initials: JG
authors.lastname: Vlachojannis
mesh_terms: D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D017403:In Situ Hybridization; D007674:Kidney Diseases / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007678:Kidney Glomerulus; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000503:physiopathology; D009994:Osmolar Concentration; D011239:Prednisolone / Q000627:therapeutic use; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012074:Remission Induction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D053773:Transforming Growth Factor beta1
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016572:Cyclosporine; D011239:Prednisolone