Bone morphogenetic protein-9 binds to liver cells and stimulates proliferation.
A new member of the transforming growth factor (TGF)-beta superfamily, BMP-9, has recently been identified and shown to be expressed in the developing mouse liver. This report demonstrates that human HepG2 liver tumor cells bind recombinant human BMP-9 (rhBMP-9) with high affinity. Cross-linking analysis indicates that HepG2 cells express two BMP-9 receptors of approximately 54 and 80 kilodaltons, similar in size to the Type I and Type II receptors reported by others for TGF-beta and BMP-4. However, cross-competition experiments demonstrate that the BMP-9 receptors on HepG2 cells do not bind other BMPs or TGF-beta s, indicating that these are novel receptors with binding specificity for BMP-9. In functional studies, rhBMP-9 stimulates HepG2 cell proliferation as indicated by [3H]thymidine incorporation and cell counting assays. A proliferative effect of rh-BMP-9 was also observed on primary rat hepatocytes. In contrast, TGF-beta had no effect on HepG2 cell proliferation and inhibited proliferation in primary hepatocytes. These results suggest that BMP-9, acting through a novel set of receptors, may play a regulatory role in hepatic growth and function.
Song
J J
JJ
Genetics Institute, Inc., Cambridge, Massachusetts 02140, USA.
Celeste
A J
AJ
Kong
F M
FM
Jirtle
R L
RL
Rosen
V
V
Thies
R S
RS
D000818:Animals; D019485:Bone Morphogenetic Proteins; D002455:Cell Division / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011506:Proteins / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D019485:Bone Morphogenetic Proteins; D006133:Growth Substances; D011506:Proteins; D011994:Recombinant Proteins; D013936:Thymidine