Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Vascular Biology Program, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts; Urological Diseases Research Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Am J Pathol. 2018 Nov;188(11):2446-2456. doi: 10.1016/j.ajpath.2018.07.016. Epub 2018 Aug 22.
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family. It contains an EGF-like domain as well as a heparin-binding domain that allows for interactions with heparin and cell-surface heparan sulfate. Soluble mature HB-EGF, a ligand of human epidermal growth factor receptors 1 and 4, is cleaved from the membrane-associated pro-HB-EGF by matrix metalloproteinase or a disintegrin and metalloproteinase in a process called ectodomain shedding. Signaling through human epidermal growth factor receptors 1 and 4 results in a variety of effects, including cellular proliferation, migration, adhesion, and differentiation. HB-EGF levels increase in response to different forms of injuries as well as stimuli, such as lysophosphatidic acid, retinoic acid, and 17β-estradiol. Because it is widely expressed in many organs, HB-EGF plays a critical role in tissue repair and regeneration throughout the body. It promotes cutaneous wound healing, hepatocyte proliferation after partial hepatectomy, intestinal anastomosis strength, alveolar regeneration after pneumonectomy, neurogenesis after ischemic injury, bladder wall thickening in response to urinary tract obstruction, and protection against ischemia/reperfusion injury to many cell types. Additionally, innovative strategies to deliver HB-EGF to sites of organ injury or to increase the endogenous levels of shed HB-EGF have been attempted with promising results. Harnessing the reparatory properties of HB-EGF in the clinical setting, therefore, may produce therapies that augment the treatment of various organ injuries.
肝素结合表皮生长因子样生长因子（HB-EGF）是表皮生长因子家族的一员。它含有一个表皮生长因子样结构域和一个肝素结合结构域，使其能够与肝素和细胞表面硫酸乙酰肝素相互作用。可溶性成熟的 HB-EGF 是人类表皮生长因子受体 1 和 4 的配体，通过基质金属蛋白酶或金属蛋白酶在一个称为外显子脱落的过程中从膜相关的前 HB-EGF 中切割出来。通过人类表皮生长因子受体 1 和 4 进行信号转导会导致多种效应，包括细胞增殖、迁移、黏附和分化。HB-EGF 水平会因不同形式的损伤以及刺激物（如溶血磷脂酸、视黄酸和 17β-雌二醇）而增加。由于它在许多器官中广泛表达，HB-EGF 在全身组织修复和再生中起着关键作用。它促进皮肤伤口愈合、部分肝切除后的肝细胞增殖、肠吻合强度、肺切除后的肺泡再生、缺血性损伤后的神经发生、尿路梗阻时膀胱壁增厚以及对许多细胞类型的缺血/再灌注损伤的保护。此外，已经尝试了一些创新的策略来将 HB-EGF 递送到器官损伤部位或增加脱落的 HB-EGF 的内源性水平，取得了有希望的结果。因此，利用 HB-EGF 的修复特性在临床环境中可能会产生增强各种器官损伤治疗的疗法。
