Hepatocyte growth factor inhibits intercellular communication via gap junctions in rat hepatocytes.
We demonstrated that HGF reduces gap junctional intercellular communication of rat hepatocyte doublets and increases cell spreading. Intercellular communication via gap junctions was markedly reduced in hepatocyte doublets with HGF (20 ng/ml) 3-12 hr after inoculation. Immunocytochemistry revealed spotty localization of connexin 32 on the plasma membrane of 3-hr cultured control hepatocyte doublets, whereas HGF-treated doublets showed significantly less connexin 32 staining. Genistein maintained intercellular communication in the presence of HGF, indicating that HGF reduces intercellular communication by down regulation of connexin 32 through the c-met/HGF receptor-tyrosine-kinase-mediated pathway. Furthermore, TGF-beta 1 maintained intercellular communication in the presence of HGF. Regulation of intercellular communication in hepatocytes by HGF and TGF-beta 1 might play an important role during liver regeneration.
Ikejima
K
K
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
Watanabe
S
S
Kitamura
T
T
Hirose
M
M
Miyazaki
A
A
Sato
N
N
D000704:Analysis of Variance; D000818:Animals; D002450:Cell Communication / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D017630:Connexins / Q000032:analysis / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D019833:Genistein; D006131:Growth Inhibitors; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D007529:Isoflavones / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D000097002:Gap Junction beta-1 Protein
D017630:Connexins; D019833:Genistein; D006131:Growth Inhibitors; D017228:Hepatocyte Growth Factor; D007529:Isoflavones; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000097002:Gap Junction beta-1 Protein