The role of transforming growth factor β during cardiovascular development

Summary

Introduction

The transforming growth factors β (TGF-βs) are a family of closely related peptides, which act on a variety of cell types, with surprisingly diverse biological actions. In addition to the TGF-βs, first isolated in 1983 (Roberts et al., 1983), there is now an ever-growing superfamily containing, the activins and inhibins, and the DVR (Z)ecapentaplegic-Vg-Related) group of growth and differentiation factors, which are found in mammals, Xenopus leavis and Drosophila melanogaster. All of these molecules are thought to be important during development (for review see Akhurst, 1994).

The TGF-β family per se has three mammalian isoforms, TGF-β1, TGF-β2 and TGF-β3, which are synthesized as precursor molecules and later cleaved to form an amino terminal latency-associated peptide and a mature carboxy terminal protein of 112 amino acids. In the biologically active region there is approximately 90% amino acid sequence homology between the three isoforms, suggesting that the different molecules should display similar biological activities (Roberts & Sporn, 1990). However, although the three isoforms have similar qualitative and quantitative effects on keratinocytes, fibroblasts, and osteoclasts, this is not always the case. TGF-β1 has been shown to be a potent inhibitor of endothelial cells in vitro (Heimark, Twardzik & Schwartz, 1986; Muller et al., 1987), whereas TGF-β2 is one to two orders of magnitude less effective as an endothelial growth inhibitor (Jennings et al., 1988; Merwin et al., 1991; Qian et al., 1992). Similarly, TGF-β2 can be an inducer of mesoderm formation in Xenopus ectodermal explants, whereas TGF-β1 only possesses the ability to potentiate the mesoderm-inducing capacity of basic fibroblast growth factor (Rosa et al, 1988).