Hepatocyte growth factor and its receptor Met are induced in crescentic glomerulonephritis.
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.
Rampino
Teresa
T
Unit of Nephrology, Dialysis and Transplantation, IRCCS Policlinico San Matteo, 27100 Pavia, Italy. t.rampino@smatteo.pv.it
Gregorini
Marilena
M
Camussi
Giovanni
G
Conaldi
Pier Giulio
PG
Soccio
Grazia
G
Maggio
Milena
M
Bottelli
Antonella
A
Dal Canton
Antonio
A
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
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