title: Hepatocyte growth factor and its receptor Met are induced in crescentic glomerulonephritis.
abstract: BACKGROUND
  In experimental extracapillary glomerulonephritis (EG) podocytes migrate, proliferate and change phenotype, and play a pivotal role in crescent formation. Hepatocyte Growth Factor (HGF) is an injury-induced effector of tissue repair that causes cell migration, growth and transdifferentiation via its receptor Met.
  
  
  METHODS
  In 11 patients with EG we measured serum levels of HGF and investigated whether serum induces the release of HGF by Peripheral Blood Mononuclear Cells (PBMC). In renal biopsies we studied the expression of Met. In cultured podocytes we studied Met expression, migration, growth and morphological changes induced by recombinant (r) HGF.
  
  
  RESULTS
  In patients with EG average serum levels of HGF (0.73 ng/ml) were higher than in normal volunteers (N, 0.10 ng/ml, p<0.01) and in patients with non-crescentic glomerular disease (GD, 0.18 ng/ml, p<0.01). Serum of EG induced a significant HGF release by PBMC (mean 0.58 ng/ml) in comparison with serum of N and GD (0.07 and 0.06 ng/ml, respectively, both p<0.001). Met was strongly expressed in crescents. Cultured podocytes expressed Met, and rHGF induced in podocytes a time- and dose-dependent migration, growth and epithelial to mesenchymal transdifferentiation.
  
  
  CONCLUSIONS
  These results suggest that HGF/Met system participates in the process of crescent formation by inducing podocyte migration, growth and mesenchymal transformation.
authors.affiliation: Unit of Nephrology, Dialysis and Transplantation, IRCCS Policlinico San Matteo, 27100 Pavia, Italy. t.rampino@smatteo.pv.it
authors.forename: Teresa
authors.initials: T
authors.lastname: Rampino
authors.forename: Marilena
authors.initials: M
authors.lastname: Gregorini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
authors.forename: Pier Giulio
authors.initials: PG
authors.lastname: Conaldi
authors.forename: Grazia
authors.initials: G
authors.lastname: Soccio
authors.forename: Milena
authors.initials: M
authors.lastname: Maggio
authors.forename: Antonella
authors.initials: A
authors.lastname: Bottelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Dal Canton
mesh_terms: D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005921:Glomerulonephritis / Q000097:blood* / Q000503:physiopathology*; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D015260:Neprilysin / Q000378:metabolism; D009504:Neutrophils; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met; D017978:Receptors, Growth Factor / Q000378:metabolism*; D011994:Recombinant Proteins
chemical_list: D015820:Cadherins; D011518:Proto-Oncogene Proteins; D017978:Receptors, Growth Factor; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D015260:Neprilysin