Current information indicates that the mammalian kidney is a significant site of
EGF synthesis, second only to the salivary gland in the rodent and probably exceeding most other tissues in the human species. The
prepro EGF mRNA is localized to the cells of the TALH and the DCT. The
EGF mRNA transcript in kidney is similar to that in salivary gland; the molecular mass of the
prepro EGF protein in kidney approximates 130,000 kDa. Several
EGF peptides are excreted in urine, including 6000-molecular weight
peptides (composed of
EGF 1-53, 1-52, 1-51, and 1-50) and a 30,000-molecular weight species with an aminoterminus portion corresponding to
amino acids 829-848 of the prepro molecule. It has been suggested that
prepro EGF could be a
membrane protein since it contains an internal hydrophobic domain (
amino acids 1039-1058) adjacent to the
EGF sequence (
amino acids 976-1029). The 30,000-molecular weight urinary product appears to represent a
protein derived from
amino acids 829 to approximately 1029 of
prepro EGF, adjacent (distal) to the hydrophobic domain. Moreover, immunoelectron microscopy localizes the
EGF immunoreactivity to the apical plasma membrane of the TALH and DCT cells. The molecular form of this apically localized,
EGF immunoreactivity is not yet clear. Proximal, distal, and TALH cells of the renal tubules and renal medullary interstitial cells appear to have
EGF receptors and respond to
EGF with increased
DNA synthesis and mitogenesis. Also, there is a relatively late increase in
prepro EGF mRNA levels in TALH and DCT cells during the process of renal
hypertrophy. Limited evidence suggests a role of
EGF on tubular function mediated via basal
EGF receptors.
EGF peptides processed intracellularly or by membrane localized
peptidases appear to be continuously excreted and secreted into urine from the apical membrane surface of the TALH and DCT cells. This urinary
EGF is constantly bathing urinary tract epithelial surfaces and could play a role in maintaining surface integrity. A similar role for salivary gland
EGF in saliva has been proposed for the gastrointestinal tract. It also is possible that
prepro EGF is anchored in the apical membrane, where it could function as a receptor, and a role for renal tubular
EGF in regulation of membrane transport events has been proposed.