Hepatocyte growth factor is a mitogen for olfactory ensheathing cells.
Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes, and it has multi-functional effects in a variety of cells in various organs. HGF stimulates DNA synthesis and promotes cell migration and morphogenesis in several cell types including the olfactory system. To characterize the potential mitogenic activity of HGF that might contribute to olfactory ensheathing cell (OEC) proliferation, we tested the ability of HGF to stimulate OEC division in vitro. OECs were obtained from adult rat olfactory bulbs and cultured in serum-free medium, and were identified by double immunostaining for p75 and S-100 antibodies. DNA synthesis assayed by pulsing BrdU for 24 hr showed that HGF at the concentration of 5-100 ng/ml elicited a 5-10-fold increase of OEC proliferation. By immunocytochemical analysis, we demonstrated that c-Met-immunoreactivity was present in cultured OECs, and c-Met anti-serum significantly sequestered the activity of HGF on OECs proliferation, suggesting that HGF-induced proliferation of OECs is mediated by the c-Met receptor. The mitogenic activity of HGF was potentiated by addition of heregulin (HRG), but inhibited by addition of forskolin. These results demonstrate that HGF is a novel mitogen for rat OECs in vitro, and HGF/c-Met system is involved in regulating OECs growth and development.
Yan
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Department of Neurology, Yale University School of Medicine, Neuroscience Research Center, VA Medical Center, West Haven, Connecticut 06516, USA.
Nie
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Kocsis
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D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016380:Brain Tissue Transplantation / Q000379:methods*; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000637:transplantation; D005576:Colforsin / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D007150:Immunohistochemistry; D008934:Mitogens / Q000494:pharmacology*; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000637:transplantation; D009830:Olfactory Bulb / Q000166:cytology / Q000187:drug effects* / Q000637:transplantation; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D020196:Trauma, Nervous System / Q000601:surgery*
D000906:Antibodies; D016895:Culture Media, Serum-Free; D005904:Glial Fibrillary Acidic Protein; D008934:Mitogens; D020800:Receptor, Nerve Growth Factor; D009418:S100 Proteins; D005576:Colforsin; D017228:Hepatocyte Growth Factor; D000242:Cyclic AMP; D019859:Proto-Oncogene Proteins c-met