Epidermal growth factor and the kidney.

Abstract

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.