[Hepatocyte growth factor (HGF) reduces the expression of profibrotic factors in human isolated glomeruli].
BACKGROUND
The imbalance between the synthesis and degradation of the mesangial matrix causes glomerulosclerosis and ultimately leads to chronic renal failure. HGF is a pleiotropic cytokine involved in angiogenesis, morphogenesis, organogenesis, and bone remodeling. Recently, we and other investigators have shown that HGF has a central role in the recovery of acute renal failure. Furthermore, HGF treatment halts the progression of kidney disease in a murine model of chronic renal failure. The aim of the present study was to evaluate the effect of HGF on the mRNA levels of molecules involved in the extracellular matrix turnover and of the c-met receptor in isolated human glomeruli.


METHODS
Human glomeruli were isolated by microdissection from donor kidney biopsies just before transplantation. Glomeruli were extensively washed and incubated with culture media containing HGF (50 ng/mL) for 24 h at 37 C. Glomeruli incubated without HGF were used as controls. After 24 h, glomeruli were washed and freezed and thawed three times. The expression of c-met, (alpha2) IV collagen, TGF-beta, metalloproteases 9 (MMP9), and of the inhibitor of metalloproteases-1, TIMP-1 was evaluated by in situ reverse transcription (RT) and polymerase chain reaction (PCR). beta-actin was used as a housekeeping gene.


RESULTS
The (alpha2)IV collagen mRNA level was decreased by HGF in human glomeruli. TGF-beta and TIMP-1 gene expression was markedly reduced by HGF treatment, whereas the expression of MMP-9 and c-met did not change. Under light-microscopic examination, kidney biopsies showed neither glomerular hypercellularity nor mesangial expansion.


CONCLUSIONS
HGF treatment reduces the expression of extracellular matrix components and of profibrotic factors in human glomeruli. Our results confirm a protective role of HGF in glomerulosclerosis.
Esposito
C
C
Unita' Operativa di Nefrologia, Dialisi e Trapianto, IRCCS Policlinico San Matteo, Universita' degli Studi di Pavia, Pavia, Italy. espositociro56@hotmail.com
Parilla
B
B
De Mauri
A
A
Cornacchia
F
F
Fasoli
G
G
Foschi
A
A
Mazzullo
T
T
Plati
A R
AR
Scudellaro
R
R
Dal Canton
A
A
D017228:Hepatocyte Growth Factor / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000378:metabolism*
D017228:Hepatocyte Growth Factor