Abstract
The vascular cell responses to the type 1, 2, and 3 isoforms of transforming growth factor‐β (TGF‐β1, TGF‐β2, TGF‐β3) were studied using bovine aortic endothelial (BAECs) and smooth muscle cells (BASMC3) as well as rat epididymal fat pad microvascular endothelia (RFCs). Three distinct bioassays indicated that TGF‐β3 elicits results that do not differ significantly from those of the TGF‐β1 isoform in all three cell populations. These assays are: inhibition of proliferation, cell migration, and neovascularization. By contrast the cellular responses to TGF‐β1 and TGF‐β3 differed from those to TGF‐β2. Three distinct receptor assays revealed the preesnce of type I and type II TGF‐β1 cell surface binding proteins on BAECs, BASMCs, and RFCs. Experimentation to decipher cell surface binding by the different isoforms revealed that iodinated TGF‐β1 bound to the surface of all three vascular cell types can be competed off in similar fashion by either TGF‐β1 or TGF‐β3; however, competition with TGF‐β2 produced unique binding profiles dependent on the cell type examined. The ratios of type I to type II TGF‐β receptors in these three vascular cell types vary from 1:1 in BAECs to 1.5:1 in RFCs to 3:1 in BASMCs and can be correlated with the differences noted in cellular responses to TGF‐β1 and TGF‐β2 in proliferation, migration, and in vitro angiogenic assays.
In summary, both the TGF‐β1 and TGF‐β3 isoforms of the transforming growth factor‐β family evoke comparable responses in proliferation, migration, angiogenic and cell surface bindinga ssays using three distinct vascular cell types, while the biofunctions of TGF‐β2 on these cells are distinct. These findings support the hypothesis that there are different responses to the TGF‐βs depending on the cell type and experimental conditions as well as the TGF‐β concentration and isoform. © 1992 Wiley‐Liss, Inc.