Stimulation of proliferation of rat hepatic stellate cells by galectin-1 and galectin-3 through different intracellular signaling pathways.
We found that the expression of galectin-1 and galectin-3 was significantly up-regulated in hepatic stellate cells (HSCs) both in the course of their transdifferentiation into myofibroblasts, a process of "self-activation," and in the fibrosis of liver tissues. Recombinant galectin-1 and galectin-3 stimulated the proliferation of cultured HSCs via the MEK1/2-ERK1/2 signaling pathway. However, galectin-3 utilized protein kinases C and A to induce this process, whereas galectin-1 did not. We also found that thiodigalactoside, a potent inhibitor of beta-galactoside binding, attenuated the effects of both galectins. In addition, galectin-1, but not galectin-3, promoted the migration of HSCs. Thus, it appears that galectin-1 and galectin-3, generated by activated HSCs, could participate in beta-galactoside binding and induce different intracellular signaling pathways leading to the proliferation of HSCs.
Maeda
Naoto
N
Department of Hepatology, Graduate School of Medicine, Osaka City University, Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
Kawada
Norifumi
N
Seki
Shuichi
S
Arakawa
Tetsuo
T
Ikeda
Kazuo
K
Iwao
Hiroshi
H
Okuyama
Hiroaki
H
Hirabayashi
Jun
J
Kasai
Ken-ichi
K
Yoshizato
Katsutoshi
K
D000818:Animals; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004730:Endothelium, Vascular / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D037483:Galectin 1 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D037502:Galectin 3 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D015870:Gene Expression; D022781:Hepatocytes / Q000737:chemistry; D006801:Humans; D007728:Kupffer Cells / Q000737:chemistry; D008099:Liver / Q000166:cytology*; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D001616:beta-Galactosidase / Q000378:metabolism
D004791:Enzyme Inhibitors; D037483:Galectin 1; D037502:Galectin 3; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D011994:Recombinant Proteins; C482128:MAP2K2 protein, human; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human; D020929:Mitogen-Activated Protein Kinase Kinases; D001616:beta-Galactosidase