Modulation of vascular cell behavior by transforming growth factors β

Abstract

The vascular cell responses to the type 1, 2, and 3 isoforms of transforming growth factor-beta (TGF-beta 1, TGF-beta 2, TGF-beta 3) 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-beta elicits results that do not differ significantly from those of the TGF-beta 1 isoform in all three cell populations. These assays are: inhibition of proliferation, cell migration, and neovascularization. By contrast the cellular responses to TGF-beta 1 and TGF-beta 3 differed from those to TGF-beta 2. Three distinct receptor assays revealed the presence of type I and type II TGF-beta 1 cell surface binding proteins on BAECs, BASMCs, and RFCs. 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 on the cell type examined. The ratios of type I to type II TGF-beta 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-beta 1 and TGF-beta 2 in proliferation, migration, and in vitro angiogenic assays.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of Transforming Growth Factor Signalling in Marrow Stem Cell Differentiation

“…This suggests that TGFβ signalling may lead to mesenchymal differentiation, more specifically, smooth muscle differentiation, as α-SMA is a marker of myofibroblast formation. This is consistent with previous literature stating that TGFβ signalling may lead to the formation of pericytes and smooth muscle cells (13)(14)(15) …”

“…In vivo studies initially indicated that TGFβ signalling inhibits endothelial proliferation and migration while stimulating the differentiation of cells into mesenchymal phenotypes, more specifically to pericytes and smooth muscle cells. (13)(14)(15). However, stimulatory effects of TGFβ have also been reported on angiogenesis in vivo (1,(16)(17).…”

Increased expression of fibronectin and the α5β1 integrin in angiogenic cerebral blood vessels of mice subject to hypobaric hypoxia

“…Angiogenesis is promoted by growth factors including vascular endothelial growth factor (VEGF) (Millauer et al, 1993;Ferrara et al, 1996), basic fibroblast growth factor (bFGF) (Klein et al, 1997), transforming growth factor beta 1 (TGF-β1) (Roberts et al, 1986;Madri et al, 1992), and the angiopoieteins (Sato et al, 1995;Maisonpierre et al, 1997). In addition to growth factors, the extracellular matrix (ECM) also plays an essential role in regulating angiogenesis and vascular remodeling (Stromblad and Cheresh, 1996;Eliceiri and Cheresh, 2001;Iivanainen et al, 2003;Stupack and Cheresh, 2003).…”

Signaling by ALK5 mediates TGF-β-induced ET-1 expression in endothelial cells: a role for migration and proliferation

“…ALK1/Smad1/5 activates cell proliferation and migration and is more related to the angiogenic state with the expression of inhibitor of DNA binding 1 (Id-1) and endoglin, among others (Byfield and Roberts, 2004;Goumans et al, 2003b;Goumans et al, 2002;Wu et al, 2006). TGF-␤ has been described to either activate or repress the process of angiogenesis (Madri et al, 1992;Roberts et al, 1986;Vinals and Pouyssegur, 2001;Yang and Moses, 1990). The existence of these receptors and their downstream responses may then reconcile contradictory TGF-␤-mediated effects observed in endothelial cells.…”