Human HB-EGF (Heparin-Binding EGF-like growth factor), also known as the DTR (diphtheria toxin receptor), is a 12-16 kDa member of the EGF family of peptide growth factors. It is further classified as a group 2 ErbB ligand based on its ability to activate both the EGF/ErbB1 and ErbB4 receptors. Mature HB-EGF is a soluble peptide that arises from proteolytic processing of the transmembrane form. The transmembrane form of HBEGF is a juxtacrine growth and adhesion factor and is uniquely the receptor for diphtheria toxin. Cells known to express HB-EGF include bronchial epithelium, visceral and vascular smooth muscle , CD4+ T cells, cardiac muscle, glomerular podocytes, keratinocytes and IL-10-secreting regulatory macrophages. HBEGF participates in diverse biological processes, including heart development and maintenance, skin wound healing, eyelid formation, blastocyst implantation, the progression of atherosclerosis, and tumor formation, through the activation of signaling molecules downstream of ErbB receptors and interactions with molecules associated with HBEGF. tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta markedly increased HB-EGF mRNA levels in HUVEC by 12- and 7-fold, respectively, and induction of the gene by TNF-alpha was both dose- and time-dependent.
