HB-EGF  (肝素结合性表皮生长因子)

肝素结合性表皮生长因子 (HB-EGF) 是 EGF 家族中与肝素结合的成员之一。它是成纤维细胞和平滑肌细胞有效的有丝分裂原和趋化因子。HB-EGF 合成为膜锚定形式 (pro-HB-EGF)，经金属蛋白酶 ADAM 家族处理释放可溶性成熟肽，这个过程被称为“外域脱落”。无论是作为膜锚定形式还是作为可溶性形式 (s-HB-EGF)，它都具有生物活性。EGF 表达于多种细胞类型，包括单核细胞/巨噬细胞、CD4+淋巴细胞、中性粒细胞、嗜酸性粒细胞、髓系白血病母细胞、骨髓瘤细胞、血管平滑肌细胞、内皮细胞和正常或肿瘤上皮细胞。 pro-HB-EGF 作为一种细胞间粘附蛋白，主要表现为抑制近分泌活性，参与细胞周期阻滞、生长抑制以及抗凋亡。HB-EGF 作为EGFR和ErbB4的天然配体，通过与受体结合发挥其活性。它参与创面愈合、心肌肥厚、平滑肌细胞增生、肾集管形态形成、囊胚植入、肺动脉高压、致瘤转化等生理和病理过程。

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a heparin-binding member of the EGF family. It is a potent mitogen and chemotactic factor for fibroblasts and smooth muscle cells. HB-EGF is synthesized as a membrane-anchored form (pro-HB-EGF) that is processed by the ADAM family of metalloproteinases to release soluble mature peptide, which as known as “ectodomain shedding”. It is biologically active either as a pro-HB-EGF or as a soluble form (s-HB-EGF). EGF is expressed in a wide range of cell types, including monocytes/macrophages, CD4+ lymphocytes, neutrophils, eosinophils, myeloid leukemia blasts, myeloma cells, vascular smooth muscle cells, endothelial and normal, or neoplastic epithelial cells. The pro-HB-EGF as a cell-to-cell adhesion protein that exerts mainly inhibitory juxtacrine activities involved in cell cycle arrest and growth inhibition as well as resistance to apoptosis. As a native ligand of EGFR and ErbB4, HB-EGF exerts its activities by binding to its receptors. It is involved in a number of physiological and pathological processes, which include wound healing, cardiac hypertrophy, smooth muscle cell hyperplasia, kidney collecting duct morphogenesis, blastocyst implantation, pulmonary hypertension, and oncogenic transformation.