Vascular cell responses to TGF-beta 3 mimic those of TGF-beta 1 in vitro.
The vascular cell responses to the type 3 isoform of transforming growth factor-beta (TGF-beta 3) were studied using bovine aortic endothelial (BAECs) and smooth muscle cells (BASMCs) as well as rat epididymal fat pad microvascular endothelia (RFCs). Four distinct bioassays indicated that TGF-beta 3 elicits results that do not differ significantly from those of the TGF-beta 1 isoform in all three cell populations. Inhibition of proliferation by TGF-beta 3 at a 5-day time point ranged from 85% on BAECs, to 55% and 53% on RFCs and BASMCs, respectively. The effects of TGF-beta 3 and TGF-beta 1 on cell migration were also found to be similar; migration of large vessel endothelial cells was inhibited 35%, while migration of smooth muscle cells was enhanced 30%. TGF-beta 1 and TGF-beta 3 also had equivalent effects on neovascularization while a 10-fold higher concentration of TGF-beta 2 was required to elicit a similar response. Experimentation to decipher cell surface binding by the different isoforms revealed that iodinated TGF-beta 1 bound to the surface of all three vascular cell types can be competed off in similar fashion by either TGF-beta 1 or TGF-beta 3; however, competition with TGF-beta 2 produced unique binding profiles dependent upon the cell type examined. In summary, both the TGF-beta 1 and TGF-beta 3 isoforms of the transforming growth factor-beta family evoke comparable responses in proliferation, migration, angiogenic and cell surface binding assays using three distinct vascular cell types, while the biofunctions of TGF-beta 2 on these cells are distinct.
Merwin
J R
JR
Department of Pathology, Yale University, New Haven, CT 06510.
Roberts
A
A
Kondaiah
P
P
Tucker
A
A
Madri
J
J
D000818:Animals; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000145:classification / Q000378:metabolism / Q000494:pharmacology*
D016212:Transforming Growth Factor beta