title: Hepatocyte growth factor (HGF) modulates matrix turnover in human glomeruli.
abstract: BACKGROUND
  The imbalance between synthesis and degradation of mesangial matrix causes glomerulosclerosis and leads to renal failure. Hepatocyte growth factor (HGF) has been shown to reduce the progression in murine models of chronic renal failure. The present study evaluated the effect of HGF on the extracellular matrix turnover and on c-met receptor in human glomeruli.
  
  
  METHODS
  Human glomeruli microdissected from donor kidney biopsies before transplantation were incubated with culture media containing HGF (50 ng/mL). After 24 and 48 hours, the expression of c-met, (alpha2) IV collagen, transforming growth factor-beta (TGF-beta), metalloprotease (MMP) 2 and 9 and of the inhibitor of MMP-2, tissue inhibitors of metalloprotease-1 (TIMP-1), was evaluated by polymerase chain reaction (PCR). beta-actin was used as housekeeping gene. The production of collagen type IV and TGF-beta was evaluated by enzyme-linked immunosorbent assay (ELISA) and Western blotting and the activity of MMP by zymography.
  
  
  RESULTS
  (alpha2) IV collagen, TGF-beta, and TIMP-1 mRNA levels were markedly decreased in glomeruli treated with HGF at 24 and 48 hours. The expression of c-met was up-regulated by HGF treatment. HGF reduced the production of collagen type IV and TGF-beta. MMP-2 but not MMP-9 mRNA level was increased in HGF-treated glomeruli, although the gelatinolytic activity of the supernatant was not changed. By light microscopic examination kidney biopsies neither showed glomerular hypercellularity nor mesangial expansion.
  
  
  CONCLUSIONS
  HGF reduced expression and synthesis of TGF-beta and collagen type IV and increased MMP-2 mRNA level in normal human glomeruli. These results suggest an antifibrotic effect of HGF on glomerular cells and may explain its beneficial role in glomerulosclerosis.
authors.affiliation: Unit of Nephrology, Dialysis and Transplantation, IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy. espositociro56@hotmail.com
authors.forename: Ciro
authors.initials: C
authors.lastname: Esposito
authors.forename: Bina
authors.initials: B
authors.lastname: Parrilla
authors.forename: Andreana
authors.initials: A
authors.lastname: De Mauri
authors.forename: Flavia
authors.initials: F
authors.lastname: Cornacchia
authors.forename: Gianluca
authors.initials: G
authors.lastname: Fasoli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Foschi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Mazzullo
authors.forename: Annarita
authors.initials: A
authors.lastname: Plati
authors.forename: Roberta
authors.initials: R
authors.lastname: Scudellaro
authors.forename: Antonio
authors.initials: A
authors.lastname: Dal Canton
mesh_terms: D024141:Collagen Type IV / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D024141:Collagen Type IV; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9