Biological effects of epidermal growth factor, with emphasis on the gastrointestinal tract and liver: An update

Abstract

Epidermal growth factor (EGF) is a 6,000 Da polypeptide hormone produced by glands of the gastrointestinal tract, namely the salivary and Brunner's glands. It is found in a wide variety of external secretions as well as in blood and amniotic fluid. In fetal and neonatal life, EGF appears to play an important role in the development of the oral cavity, lungs, gastrointestinal tract and eyelids. Its presence in cells of the central nervous system suggests that it also plays a role in modulating the development of this system. In adult animals, the function of EGF is much less well understood. In rodents, it apparently modulates acid secretion from parietal cells in the stomach, and it undoubtedly plays an important role in wound healing, either through its localization within skin or by the licking of wounds with EGF-containing saliva. Considerable evidence now suggests that it may be one of the key factors in initiating liver regeneration after partial hepatectomy or chemical injury. The liver appears to be the principal organ which regulates the circulating level of EGF. In fact, EGF is cleared so efficiently by the liver that only the peripheral cells of the lobule (zone 1) sequester EGF, and little remains in the circulation for cells in the more distal zones (zones 2 and 3). In the liver, EGF normally binds to a plasma membrane receptor and is internalized within the liver cell, where the vast majority of EGF and its receptor are destroyed in lysosomes. A small but consistent quantity of EGF enters the bile intact. In the regenerating liver, however, the lysosomal pathway appears to be shut down, and the EGF is diverted to hepatocyte nuclei prior to the initiation of DNA synthesis. Nuclear EGF is found free as well as bound to a high-molecular-weight protein which has many characteristics identical to the plasma membrane EGF receptor. The plasma membrane receptor is a large transmembrane glycoprotein of 170,000 Da containing four domains: an extracellular EGF-binding portion, a hydrophobic membrane-spanning segment, a proximal cytoplasmic domain which binds ATP and protein substrates containing tyrosine for phosphorylation and a terminal cytoplasmic portion with 3 tyrosines which undergo autophosphorylation after EGF binding.(ABSTRACT TRUNCATED AT 400 WORDS)

Different Epidermal Growth Factor Receptor (EGFR) Agonists Produce Unique Signatures for the Recruitment of Downstream Signaling Proteins

“…In vivo levels of EGF and other ErbB family growth factors vary widely from tissue to tissue, being low in plasma but 10 -100-fold higher in secretions such as saliva and tears (33)(34)(35). Given the differences in network behavior identified here, our data imply that therapeutic agents that target one particular node in the signaling pathway could be efficacious in one tissue but not in another, simply because of differences in network utilization based on the identity of the stimulating growth factor and/or the dose involved.…”

EGF and HGF levels are increased during active HBV infection and enhance survival signaling through extracellular matrix interactions in primary human hepatocytes

“…The major source of EGF for the liver is thought to be Brunner's gland in the duodenum. 37 EGF is taken up by the liver in one pass and deposited periportally. 37 Serum levels rise only slightly after partial hepatectomy; however, there is abundant evidence that EGF plays a critical role in liver regeneration.…”

“…37 EGF is taken up by the liver in one pass and deposited periportally. 37 Serum levels rise only slightly after partial hepatectomy; however, there is abundant evidence that EGF plays a critical role in liver regeneration. [38][39][40] We thus may have underesti- mated the rise in the bioavailable EGF and HGF in the liver of patients as we measured peripheral plasma levels.…”

Impact of hypertension in liver regeneration in rats

“…However, hepatocytes are the first to proliferate and most studies highlight these cells because they constitute about 90% of hepatic mass and 60% of total cells 1,2 . The hepatocyte is an epithelial nature cell, stable, highly differentiated, which rarely divides 3 .…”