Platelet-derived growth factor expression in a transgenic model.

Abstract

The migration, proliferation and organization of cells in tissues are controlled by several forms of intercellular communication. One form of control involves a network of diffusible polypeptide growth factors that activate membrane receptors and transduce proliferative signals. One of these growth factors, platelet-derived growth factor (PDGF), has provided a framework for understanding the cellular and molecular events that underlie the biological effects of a number of growth factors. PDGF is a family of several closely related 30 kDa dimers consisting of two disulfide-bonded polypeptide chains, designated A and B [reviewed in 1]. All three isoforms of PDGF (AA-, AB- and BB) are biologically active. Two distinct PDGF receptors have been identified: one that binds either to the A- or the B-chain (the α subunit) and one that binds only the B-chain (the β subunit) [reviewed in 2]. The capacity of cells to respond to PDGF depends upon the presence of a particular dimeric form of PDGF as well as expression of appropriate receptors. PDGF is both mitogenic and chemotactic for cells such as fibroblasts, smooth muscle cells and glial cells [reviewed in 3]. Because of these properties, PDGF has been implicated in stimulating the proliferation and cell movement of cells in normal developmental and reparative responses (for example, wound healing), as well as in pathologic processes, such as atherosclerosis and neoplasia. However, there is little compelling evidence that PDGF actually plays a critical role in any of these processes in vivo. To fully evaluate the possible functions of PDGF, a detailed description of ligand production, as well as PDGF receptor expression, is required in each of these settings. Surprisingly, such documentation is only preliminary. Standard approaches to localize PDGF expression in vivo have employed either immunohistochemistry or in situ hybridization. However, these methods have several potential disadvantages: first, PDGF is a secreted protein, which implies that cytoplasmic levels of the protein in intact animals may be low; second, isoform-specific antibodies which cross species are not readily available; and third, transcript levels of PDGF B-chain may be low in vivo because the mRNA has a short half-life. To circumvent these potential problems, a different approach was taken.