Distribution of heparin-binding EGF-like growth factor protein and mRNA in the normal rat kidneys

Heparin-binding EGF-like growth factor (HB-EGF), a newly discovered potent 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 synthesized digoxigenin-labeled anti-sense riboprobe of HB-EGF. Immunohistochemical and in situ hybridization studies revealed that the tubular epithelial cells of the S3 segment of the outer stripe in the outer medulla were the predominant renal source of HB-EGF. In addition, in the immunohistochemical analysis, HB-EGF was ubiquitously present in the epithelial cells of the proximal tubules and the arterial smooth muscle cells, while HB-EGF expression was not detected in other parts of the kidney, including the glomeruli. Although EGF receptors were found to be 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 proximal 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.