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Heparin-binding epidermal growth factor (HB-EGF) is a member of the EGF family that binds to heparin. It is a potent mitogen and chemokine for fibroblasts and smooth muscle cells. HB-EGF is synthesized in a membrane-anchored form (pro-HB-EGF), which is processed by the ADAM family of metalloproteases to release the soluble mature peptide, a process termed "ectodomain shedding". It is biologically active both as a membrane-anchored form and as a soluble form (s-HB-EGF). HB-EGF is involved in physiological and pathological processes such as wound healing, cardiac hypertrophy, smooth muscle cell proliferation, renal duct morphogenesis, blastocyst implantation, pulmonary hypertension, and tumorigenic transformation.