Collagenase pretreatment and the mitogenic effects of hepatocyte growth factor and transforming growth factor-alpha in adult rat liver.
Hepatocyte growth factor and transforming growth factor-alpha are two well-known hepatomitogens for primary hepatocyte cultures. Here we report that these two growth factors also stimulate in vivo DNA syntheses in normal, unoperated, adult rat liver after 24-hr continuous intraportal infusion. As determined by an immunohistochemical staining technique, 5-bromo-2'-deoxyuridine incorporation was increased in a dose-dependent fashion after infusion of up to 10 micrograms of growth factor/100 gm body weight in the rat. Stimulation of DNA synthesis was seen in the periportal area. Pretreatment using intraportal infusion of collagenase (1 U/kg body weight) for 4 hr before administration of growth factor increased the labeling by 2- to 4-fold to a labeling index range of 48% to 52%. These results suggest that collagenases and possibly other proteases are involved in making hepatocytes competent to respond to growth factors at very early stages of liver regeneration.
Liu
M L
ML
Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Mars
W M
WM
Zarnegar
R
R
Michalopoulos
G K
GK
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D017364:Collagenases / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D016211:Transforming Growth Factor alpha; D017228:Hepatocyte Growth Factor; D004247:DNA; D017364:Collagenases