Connective Tissue Formation in Wound Healing - E-thesis

The various isoforms of PDGF have different mitogenic and chemotactic activity. Vascular
smooth muscle cells (SMC) and fibroblasts express both α- and β- receptors. On SMC, PDGF-
AA initiates cellular hypertrophy, while BB induces hyperplasia (351). On fibroblasts, the BB
isoform initiates chemotaxis, while AA inhibits chemotaxis (352, 353). PDGF binds to several
plasma proteins and also to proteins of the extracellular matrix which facilitates local
concentration of the factor. The factor functions as a local autocrine and paracrine growth
factor (256). PDGF may act as an immunomodulator by up-regulating intercellular adhesion
molecule 1(ICAM-1) in SMC, and inducing transient IL-2 secretion in T cells, and down-
regulating of IL-4 and IFN-γ production (354, 355).
PDGF is one of several factors that stimulate the healing of soft tissues (10, 356). PDGF is a
potent mitogen for connective tissue cells, and in addition, it stimulates chemotaxis of
fibroblasts, SMC, neutrophils, and macrophages (256). PDGF has the ability to activate
macrophages to produce and secrete other growth factors of importance for various aspects of
the healing process. PDGF stimulates the production of fibronectin (357) and hyaluronic acid
(358) by fibroblasts. PDGF might be important in the later remodeling phase of wound healing,
since it stimulates the production and secretion of collagenase in fibroblasts (359).
Fibroblasts and SMC of resting tissues contain low levels of PDGF receptors. However, the
PDGF-β receptor is up-regulated in conjunction with inflammation, for example, thereby
making cells to response to PDGF (360-362). In addition to expression of PDGF-β receptors
on connective tissue cells after cutaneous injury, expression has also been noticed on epithelial
cells (363). PDGF has a weak angiogenic activity and PDGF receptors are missing from
endothelial cells of large vessels. Instead, they exist on capillary endothelial cells and on
microvascular pericytes (364, 365). However, PDGF may stimulate angiogenesis in an indirect
way, by inducing the secretion of endothelial cell growth factors by myofibroblasts (366).
Anyhow, the angiogenic effect of PDGF is weaker than that of other growth factors, e.g., of the
FGF family (367).
CTGF
Connective tissue growth factor (CTGF) belongs to the CCN (Connective tissue growth
factor/Cysteine-rich 61/Nephroblastoma overexpressed) protein family (368, 369) (Table VI
and Fig. 10.). The prototypic members of this family were discovered in the early 1990s and
were initially classified as immediate early gene products or growth factors (370-372). These
highly conserved cysteine-rich proteins share four conserved modular domains with sequence
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