Growth factors - Pharmaceutical Biotechnology: Concepts and Aapplications - page 284

IGFs are often localized within various areas of the kidney. Direct infusion of IGF-I infl uences
(usually enhances) renal function by a number of means, including promoting increased:

• glomerular fi ltration rate;

• renal plasma fl ow;

• kidney size and weight.

These responses are obviously mediated by multiple effects on the growth and activity of several
renal cell types, suggesting that IGFs play a physiological role in regulating renal function. Not
surprisingly, IGF-I is currently being assessed as a potential therapeutic agent in the treatment of
various forms of kidney disease.
IGF-I is widely expressed in the central nervous system. IGF-II is also present, being produced
mainly by tissues at vascular interfaces with the brain. Both growth factors, along with insulin,
play a number of important roles in the nervous system. They stimulate the growth and develop-
ment of various neuronal populations and promote neurotrophic effects (discussed later) and may,
therefore, be of potential use in the treatment of various neurodegenerative diseases.

10.3.3 Epidermal growth factor

EGF, a 6 kDa, 53 amino acid unglycosylated peptide, was one of the fi rst growth factors dis-
covered. Its existence was initially noted in the 1960s, as a factor present in saliva which could
promote premature tooth eruption and eyelid opening in neonatal mice. EGF has subsequently
proven to exert a powerful mitogenic effect on many cell types, and its receptor (Figure 10.7) is
expressed by most cells. Its infl uence on endothelial cells, epithelial cells and fi broblasts is par-
ticularly noteworthy, and the skin appears to be its major physiological target. It stimulates growth

EGF-binding domain

Cysteine-rich
domains

Plasma membrane

Tyrosine kinase
domain

Cytoplasm

Actin-binding
domain

Figure 10.7 The EGF receptor. The N-terminal, extracellular region of the receptor contains 622 amino acids.
It displays two cysteine-rich regions, between which the ligand-binding domain is located. A 23 amino acid
hydrophobic domain spans the plasma membrane. The receptor cytoplasmic region contains some 542 amino
acids. It displays a tyrosine kinase domain, which includes several tyrosine autophosphorylation sites, and an
actin-binding domain that may facilitate interaction with the cell cytoskeleton