Differential expression of hepatocyte growth factor, transforming growth factor-alpha and transforming growth factor-beta 1 messenger RNAs in two experimental models of liver cell proliferation.
Hepatocyte growth factor, a potent hepatocyte mitogen in vitro, appears to trigger hepatocyte regeneration after partial hepatectomy and after acute liver cell necrosis. Transforming growth factor-alpha and transforming growth factor-beta 1 may also be involved in the control of liver regeneration. In this study we assessed possible roles of hepatocyte growth factor, transforming growth factor-alpha and transforming growth factor-beta 1 on liver cell proliferation in vivo, using a model of choline deficiency that is associated with liver cell necrosis and a model of a hypolipidemic agent (4-chloro-6-(2,3 xylidino)-2-pyrimidinylthio (N-beta-hydroxyethyl) acetamide) without liver necrosis. Male F344 rats were fed a choline-deficient diet or 0.16% 4-chloro-6-(2,3 xylidino)-2-pyrimidinylthio (N-beta-hydroxyethyl) acetamide diet for 6 and 4 wk, respectively. Rats were killed periodically, and the expression of hepatocyte growth factor messenger RNA in the liver, lung and kidney was determined by Northern-blot analysis. The levels of transforming growth factor-alpha and transforming growth factor-beta 1 messenger RNAs in the liver were also determined. Feeding a choline-deficient diet for 1 to 6 wk led to gradual increases in the levels of hepatocyte growth factor, transforming growth factor-alpha and transforming growth factor-beta 1 messenger RNAs in the liver. Feeding a 4-chloro-6-(2,3 xylidino)-2-pyrimidinylthio (N-beta-hydroxyethyl) acetamide diet for 3 days and 2 wk induced marked enhancement of liver cell proliferation as judged by hepatocyte 5-bromo-2-deoxyuridine incorporation.(ABSTRACT TRUNCATED AT 250 WORDS)
Masuhara
M
M
Department of Pathology, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Katyal
S L
SL
Nakamura
T
T
Shinozuka
H
H
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology*; D002796:Choline Deficiency / Q000378:metabolism; D015342:DNA Probes; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000502:physiology; D000960:Hypolipidemic Agents / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009929:Organ Size; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D016211:Transforming Growth Factor alpha / Q000235:genetics* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000502:physiology
D015342:DNA Probes; D000960:Hypolipidemic Agents; D011743:Pyrimidines; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; C016908:pirinixil