Regional distribution of heparin-binding epidermal growth factor-like growth factor mRNA and protein in adult rat forebrain.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a recently described member of the EGF family that binds to and stimulates phosphorylation of the EGF receptor (EGFR). In this study, we examined the cellular localization of HB-EGF gene transcripts and protein in adult rat forebrain. In situ hybridization studies showed that neurons in various regions, including cortex, hippocampus, and deep structures, express HB-EGF mRNA. Positively labeled cells were also present in white matter, which suggests that both neurons and glia express HB-EGF mRNA. Immunohistochemical studies with an antibody specific to proHB-EGF, a transmembrane form of HB-EGF, demonstrated ubiquitous immunoreactivity in neurons and glial cells in white matter. In view of the wide expression of its cognitive receptor, EGFR, in central nervous system neurons, our results suggest that HB-EGF is an endogenous ligand for EGFR in the central nervous system and may play an important role in physiological conditions.