Distinct morphological and mito-inhibitory effects induced by TGF-beta 1, HGF and EGF on mouse, rat and human hepatocytes.
TGF-beta 1 is known as a potent inhibitor of proliferation of rat and human hepatocytes. In this study we show that the effects of TGF-beta 1 are quite different on mouse hepatocytes. In rat and human hepatocytes, TGF-beta 1 inhibited DNA synthesis and also inhibited the morphological changes induced by growth factors in rat and human hepatocytes. In contrast, addition of TGF-beta 1 to mouse hepatocytes resulted in pronounced alterations in morphology of these cells. These changes were similar to those induced by HGF and EGF. The induction of structural changes by TGF-beta 1 was noted only in mouse hepatocytes. Mouse hepatocytes were also much more resistant to the mito-inhibitory effect of TGF-beta 1. These findings suggest profound differences in hepatocyte growth regulation between these species and may relate to observed differences in susceptibility to carcinogenesis.
Petersen
B
B
Department of Pathology, University of Pittsburgh, School of Medicine, PA 15261.
Yee
C J
CJ
Bowen
W
W
Zarnegar
R
R
Michalopoulos
G K
GK
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000648:ultrastructure; D003599:Cytoskeleton / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005260:Female; D019833:Genistein; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D019311:Staurosporine; D013449:Sulfonamides / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D000470:Alkaloids; D003598:Cytoskeletal Proteins; D007529:Isoflavones; D013449:Sulfonamides; D016212:Transforming Growth Factor beta; C049999:N-(6-phenylhexyl)-5-chloro-1-naphthalenesulfonamide; D004815:Epidermal Growth Factor; D017228:Hepatocyte Growth Factor; D003513:Cycloheximide; D019833:Genistein; D019311:Staurosporine