Lobb R R
Center for Biochemical and Biophysical Sciences, Harvard Medical School, Boston, Massachusetts.
Eur J Clin Invest. 1988 Aug;18(4):321-36. doi: 10.1111/j.1365-2362.1988.tb01020.x.
The family of HBGFs represents one of the most important families of mediators yet described, capable of inducing mesenchymal cell proliferation and differentiation, tissue regeneration, morphogenesis, and neovascularization, and it is clear their clinical potential is enormous. While some obvious applications of HBGFs, such as in wound healing and seeding of vascular prostheses, are already being examined in detail, the realization of their full clinical potential will require the co-ordinated efforts of many laboratories in a wide spectrum of fields. A better understanding is needed of the pathophysiological roles of HBGFs in vivo. For example, if abnormal expression of HBGFs is the cause of certain pathologies characterized by abnormal vascularization, the clinical potential of HBGF antagonists as inhibitors of angiogenesis will be considerable. A better understanding is also needed of the relationship between HBGF structure and function, susceptibility to proteolysis, in-vivo stability, and synergism with other biological response modifiers. In addition, many clinical applications will be limited by our ability to target HBGFs to selected sites in the body, while others will be limited by undesirable side-effects. Indeed, the minimization of such side-effects may rapidly become a central issue in the in-vivo use of HBGFs. For example, the presence of HBGFs in ocular tissues, their role in phototransduction, their ability to induce neovascularization, and the clear link between abnormal ocular neovascularization and blindness, suggest that the eye may be an organ particularly sensitive to local changes in HBGF levels. Finally, HBGFs will almost certainly have extremely potent immunoregulatory effects. Nevertheless, the application of HBGFs in a variety of clinical situations should lead to many innovative therapeutic advances.
肝素结合生长因子（HBGFs）家族是迄今所描述的最重要的介质家族之一，能够诱导间充质细胞增殖和分化、组织再生、形态发生和新血管形成，显然其临床潜力巨大。虽然HBGFs的一些明显应用，如伤口愈合和血管假体植入，已经在详细研究中，但要实现其全部临床潜力需要众多实验室在广泛领域的协同努力。需要更好地了解HBGFs在体内的病理生理作用。例如，如果HBGFs的异常表达是某些以血管异常形成为特征的病理状况的原因，那么HBGF拮抗剂作为血管生成抑制剂的临床潜力将相当大。还需要更好地了解HBGF的结构与功能、对蛋白水解的敏感性、体内稳定性以及与其他生物反应调节剂的协同作用之间的关系。此外，许多临床应用将受到我们将HBGFs靶向体内特定部位能力的限制，而其他应用将受到不良副作用的限制。事实上，将此类副作用降至最低可能很快成为HBGFs体内应用的核心问题。例如，HBGFs在眼组织中的存在、它们在光转导中的作用、它们诱导新血管形成的能力以及异常眼部新血管形成与失明之间的明确联系，表明眼睛可能是一个对HBGF水平局部变化特别敏感的器官。最后，HBGFs几乎肯定具有极强的免疫调节作用。尽管如此，HBGFs在各种临床情况下的应用应该会带来许多创新性的治疗进展。
