Regional expression of hepatocyte growth factor/c-met in experimental renal hypertrophy and hyperplasia.
Hepatocyte growth factor (HGF) and its high-affinity receptor, c-met, have been found to increase in the whole kidney of the rat following several types of renal injury or renal hypertrophy. In an attempt to determine whether the upregulation of this growth factor and its receptor is selective for the regions of greatest anatomic change, and therefore likely to be important in regulating renal tubular hyperplasia and/or hypertrophy, we examined their expression in liver, whole kidney, and subsections of the kidney following either sham operation, transient ischemia of one kidney, or unilateral nephrectomy. The message for HGF was increased in both liver and kidney by all surgical procedures tested, including sham operation, and was seen predominantly in the outer cortex, the site of least morphological change. However, c-met was not upregulated by sham operation or in the liver, but rather was selectively upregulated only in the kidney in both the hypertrophy and hyperplasia (ischemia/reflow) models. Renal subsections revealed that this increase was confined to the renal medulla, with the greatest change in the outer medulla. Thus induction of the message for HGF can occur nonselectively and at sites distant to the injurious stimulus, whereas the target for HGF, c-met, is upregulated selectively at the site of greatest tubular injury or hypertrophy. These results support a role for HGF/c-met in regulation of these renal tubular events.
Joannidis
M
M
Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215.
Spokes
K
K
Nakamura
T
T
Faletto
D
D
Cantley
L G
LG
D000818:Animals; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism*; D006965:Hyperplasia; D006984:Hypertrophy; D007511:Ischemia / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000473:pathology*; D008297:Male; D019859:Proto-Oncogene Proteins c-met; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012079:Renal Circulation; D015424:Reperfusion; D014018:Tissue Distribution; D015854:Up-Regulation
D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases