Growth factors - Pharmaceutical Biotechnology: Concepts and Aapplications - page 285

Table 10.11 Range of cells producing PDGF, and its major biological activities

Synthesized by Platelets Macrophages

Fibroblasts Endothelial cells

Astrocytes Megakaryocytes

Myoblasts Kidney epithelial cells

Vascular smooth muscle cells Many transformed cell types

Biological activities
mitogen for:

Fibroblasts Variety of transformed cells

Smooth muscle cells Glial cells

chemoattractant for:

Fibroblasts Monocytes

Neutrophils Smooth muscle cells

of the epidermal layer. Along with several other growth factors, EGF plays a role in the wound
healing process, rendering a potential medical application obvious.
EGF may also fi nd a novel agricultural application in the defl eecing of sheep. Administration
of EGF to sheep has a transient effect on the wool follicle bulb cell, which results in a weakening
of the root that holds the wool in place. Although novel, this approach to defl eecing is unlikely to
be economically attractive.

10.3.4 Platelet-derived growth factor

PDGF is a polypeptide growth factor that is sometimes termed osteosarcoma-derived growth fac-
tor or glioma-derived growth factor. It was fi rst identifi ed over 20 years ago as being the major
growth factor synthesized by platelets. It is also produced by a variety of cell types. PDGF exhibits
a mitogenic effect on fi broblasts, smooth muscle cells and glial cells, and exerts various additional
biological activities (Table 10.11).
PDGF plays an important role in the wound healing process. It is released at the site of damage
by activated platelets, and acts as a mitogen/chemoattractant for many of the cells responsible for
initiation of tissue repair. It thus tends to act primarily in a paracrine manner. It also represents an
autocrine/paracrine growth factor for a variety of malignant cells.
Active PDGF is a dimer. Two constituent polypeptides, A and B, have been identifi ed, and
three active PDGF isoforms are possible: AA, BB and AB. Two slightly different isoforms of the
human PDGF A polypeptide (generated by differential mRNA splicing) have been identifi ed. The
short A form contains 110 amino acids and the long form contains 125 amino acids. Both exhibit
one potential glycosylation site and three intrachain disulfi de bonds. Two PDGF receptor subunits
have been identifi ed. Both are transmembrane glycoproteins whose cytoplasmic domains display
tyrosine kinase activity upon activation.
In vitro and in vivo studies support the thesis that PDGF is of value in wound management,
particularly with regard to chronic wounds. All three isoforms of PDGF are available from a range
of recombinant systems. In vitro studies, using various cell lines, suggest that PDGF AB or BB
dimeric isoforms are the most potent.