Modulation of vascular cell behavior by transforming growth factors beta.

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.