PMID- 9274855
OWN - NLM
STAT- MEDLINE
DCOM- 19970911
LR  - 20031114
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 77
IP  - 2
DP  - 1997 Aug
TI  - Renal tubular hyperplasia, polycystic disease, and glomerulosclerosis in 
      transgenic mice overexpressing hepatocyte growth factor/scatter factor.
PG  - 131-8
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) has been implicated as a 
      renotrophic agent, capable of stimulating renal regeneration after unilateral 
      nephrectomy or acute kidney failure. However, evaluation of the therapeutic 
      utility of HGF/SF requires thorough analysis of its effects in an appropriate in 
      vivo model system. To this end, the renal structure and function in HGF/SF 
      transgenic mice were examined. Mice overexpressing HGF/SF in the kidney and serum 
      demonstrated prominent tubular cystic disease and progressive glomerulosclerosis, 
      and were susceptible to premature death from renal failure. The tubular phenotype 
      appeared to result from HGF/SF-Met autocrine stimulation of the tubular 
      epithelium and consequent hyperplasia. Electron microscopic examination of 
      glomeruli, which also showed enhanced cellular proliferation, revealed 
      ultrastructural features consistent with focal segmental glomerulosclerosis: an 
      increase in mesangial matrix, effacement of foot processes, and thickening of 
      basement membrane. These changes were not present at birth but developed 
      progressively with age, which is consistent with the notion that HGF/SF may not 
      be essential for the early stages of nephrogenesis, but may play an important 
      role in renal epithelial renewal and regeneration. Thus, HGF/SF transgenic mice 
      could be a useful model for dissecting the molecular mechanisms leading to 
      polycystic disease and focal segmental glomerulosclerosis. Moreover, our results 
      suggest that caution should be used when considering HGF/SF as a future 
      therapeutic agent.
FAU - Takayama, H
AU  - Takayama H
AD  - Laboratory of Molecular Biology, National Cancer Institute, National Institutes 
      of Health, Bethesda, Maryland 20892-4255, USA.
FAU - LaRochelle, W J
AU  - LaRochelle WJ
FAU - Sabnis, S G
AU  - Sabnis SG
FAU - Otsuka, T
AU  - Otsuka T
FAU - Merlino, G
AU  - Merlino G
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 67256-21-7 (Hepatocyte Growth Factor)
SB  - IM
MH  - Animals
MH  - Female
MH  - Hepatocyte Growth Factor/*physiology
MH  - Hyperplasia
MH  - Kidney Glomerulus/*pathology
MH  - Kidney Tubules/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Polycystic Kidney Diseases/*etiology
EDAT- 1997/08/01 00:00
MHDA- 1997/08/01 00:01
CRDT- 1997/08/01 00:00
PHST- 1997/08/01 00:00 [pubmed]
PHST- 1997/08/01 00:01 [medline]
PHST- 1997/08/01 00:00 [entrez]
PST - ppublish
SO  - Lab Invest. 1997 Aug;77(2):131-8.