Activins A, AB, and B inhibit hepatocyte growth factor synthesis by MRC-5 human lung fibroblasts.
The effect of activins A, AB, and B on hepatocyte growth factor (HGF) synthesis stimulated by 12-O-tetradecanoylphorbol beta-acetate (TPA) was studied in MRC-5 human lung fibroblasts. Activins A, AB, and B inhibited the increase in HGF secretion induced by TPA in different dose-dependent manners and potencies. At 5 ng/ml, activins A and AB inhibited the increase approximately 30% and 10%, respectively, and at 25 ng/ml both activins produced almost maximal inhibition, i.e., approximately 40%. Activin B caused 10% inhibition at 12 ng/ml, and at 25 ng/ml produced almost maximal inhibition, approximately 30%. Further analysis with activin A indicated that the inhibition was caused by decreased HGF mRNA levels, followed by decreased cellular HGF levels. At 25 ng/ml, activin A inhibited the increase in HGF in the cellular lysate and the increase in HGF mRNA level approximately 80% and 40%, respectively.
Niimi
Shingo
S
Division of Biological Chemistry and Biologicals, National Institute of Health Sciences, Tokyo, Japan. niimi@nihs.go.jp
Hyuga
Masashi
M
Kazama
Hiromi
H
Inagawa
Masami
M
Seki
Taiichiro
T
Ariga
Toyohiko
T
Kobayashi
Tetsu
T
Hayakawa
Takao
T
D028341:Activins / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D002460:Cell Line; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006801:Humans; D028322:Inhibin-beta Subunits / Q000494:pharmacology* / Q000502:physiology; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013552:Swine
C422405:activin A; C044147:activin B; C103008:inhibin beta A subunit; D028341:Activins; D017228:Hepatocyte Growth Factor; D028322:Inhibin-beta Subunits