DISTRIBUTION OF HEPARIN-BINDING EGF-LIKE GROWTH-FACTOR PROTEIN AND MESSENGER-RNA IN THE NORMAL RAT KIDNEYS

Heparin-binding EGF-like growth factor (HB-EGF), a newly discovered po tent mitogen and chemoattractant for smooth muscle cells, is a member of the EGF superfamily and binds to EGF receptors. To investigate the role of HB-EGF in the kidney, we determined the distribution of HB-EGF immunohistochemically in normal rat kidneys. The localization of mRNA expression was also studied by in situ hybridization, using a synthes ized digoxigenin-labeled anti-sense riboprobe of HB-EGF. Immunohistoch emical and in situ hybridization studies revealed that the tubular epi thelial cells of the S3 segment of the outer stripe in the outer medul la were the predominant renal source of HB-EGF. In addition, in the im munohistochemical analysis, HB-EGF was ubiquitously present in the epi thelial cells of the proximal tubules and the arterial smooth muscle c ells, while HB-EGF expression was not detected in other parts of the k idney, including the glomeruli. Although EGF receptors were found to b e present in the proximal tubules as well as in the distal tubules and collecting ducts, EGF has not been found to be expressed in the proxi mal tubules. Therefore, the present results indicate that HB-EGF might be a ligand for EGF receptors in the proximal tubules and might play a role in the functions of proximal tubules.