Mechanism of Action and In Vivo Role of Platelet-Derived Growth Factor

1999 ◽  
Vol 79 (4) ◽  
pp. 1283-1316 ◽  
Author(s):  
Carl-Henrik Heldin ◽  
Bengt Westermark
Keyword(s):  
Growth Factor ◽  
Protein Tyrosine Kinase ◽  
Growth Stimulation ◽  
Receptor Activation ◽  
Platelet Derived Growth Factor ◽  
Cellular Effects ◽  
Structural And Functional Properties ◽  
Stimulation Of

Platelet-derived growth factor (PDGF) is a major mitogen for connective tissue cells and certain other cell types. It is a dimeric molecule consisting of disulfide-bonded, structurally similar A- and B-polypeptide chains, which combine to homo- and heterodimers. The PDGF isoforms exert their cellular effects by binding to and activating two structurally related protein tyrosine kinase receptors, denoted the α-receptor and the β-receptor. Activation of PDGF receptors leads to stimulation of cell growth, but also to changes in cell shape and motility; PDGF induces reorganization of the actin filament system and stimulates chemotaxis, i.e., a directed cell movement toward a gradient of PDGF. In vivo, PDGF has important roles during the embryonic development as well as during wound healing. Moreover, overactivity of PDGF has been implicated in several pathological conditions. The sis oncogene of simian sarcoma virus (SSV) is related to the B-chain of PDGF, and SSV transformation involves autocrine stimulation by a PDGF-like molecule. Similarly, overproduction of PDGF may be involved in autocrine and paracrine growth stimulation of human tumors. Overactivity of PDGF has, in addition, been implicated in nonmalignant conditions characterized by an increased cell proliferation, such as atherosclerosis and fibrotic conditions. This review discusses structural and functional properties of PDGF and PDGF receptors, the mechanism whereby PDGF exerts its cellular effects, and the role of PDGF in normal and diseased tissues.

scholarly journals Evidence for glutathione involvement in platelet-derived growth-factor-mediated signal transduction

1997 ◽  
Vol 324 (3) ◽  
pp. 791-796 ◽  
Author(s):  
Stefania RIGACCI ◽  
Teresa IANTOMASI ◽  
Patrizia MARRACCINI ◽  
Andrea BERTI ◽  
Maria Teresa VINCENZINI ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Activation ◽  
Platelet Derived Growth Factor ◽  
Glutathione Depletion ◽  
Physiological Processes ◽  
Buthionine Sulphoximine ◽  
Precise Relationship

Recent studies show that glutathione, while being involved in the well-known physiological processes of amino acid transport and detoxification, can also play a part in cell proliferation events. Cell treatment with l-buthionine sulphoximine, which causes glutathione depletion, is accompanied by a decrease in cell proliferation. At present no precise relationship between this thiol and any critical intermediate of the mitogenic cascade has been proved. In this study, conducted on NIH/3T3 murine fibroblasts, we demonstrate a strict correlation between glutathione levels and platelet-derived growth-factor-receptor activation in response to stimulation and cell proliferation. The receptor autophosphorylation is severely impaired at low glutathione cellular levels. The interaction of glutathione with this growth-factor receptor in vivo, while being rather specific, is complex and may involve both cytosolic and extracellular receptor domains.

scholarly journals Ischemia Induces the Expression of the Platelet-Derived Growth Factor-B Chain in Neurons and Brain Macrophages in vivo

1994 ◽  
Vol 14 (5) ◽  
pp. 818-824 ◽  
Author(s):  
Koji Iihara ◽  
Masakiyo Sasahara ◽  
Nobuo Hashimoto ◽  
Yoshihiko Uemura ◽  
Haruhiko Kikuchi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Healing Process ◽  
Focal Ischemia ◽  
Platelet Derived Growth Factor ◽  
Northern Analysis ◽  
Brain Macrophages ◽  
Tandem Occlusion ◽  
The Brain

To elucidate the role of the platelet-derived growth factor (PDGF)–B chain in the brain, we examined its expression in rat brains with focal ischemia. Focal ischemia was induced by permanent tandem occlusion of the middle cerebral and common carotid arteries in spontaneously hypertensive rats (SHRs). Northern analysis demonstrated that ischemia transiently increased mRNA expression of the PDGF–B chain, but not the PDGF–A chain, in the injured neocortex. The larger transcript (3.5 kb) of the B chain gradually increased to threefold by 16 h, whereas the smaller transcript (2.6 kb) of the B chain markedly increased sixfold by 4 h. Immunohistochemistry revealed enhanced immunoreactivity in the neurons in the infarct and in the periinfarct area from 16 h to days 4–7, with a peak at 24 h. Furthermore, the brain macrophages that accumulated in the infarct showed intense immunostaining in their perinuclear region from days 2 to 14, with a peak at days 5–6. The present study demonstrates that ischemia induces the expression of the PDGF–B chain, first in neurons and later in brain macrophages, and suggests an important role of the PDGF–B chain in the healing process of the injured brain.

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