The discovery of hepatocyte growth factor (HGF) and its significance for cell biology, life sciences and clinical medicine.
The discovery of hepatocyte growth factor (HGF) and its significance for cell biology, life sciences and clinical medicine.
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DOI：
10.2183/pjab.86.588
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Mizuno S
中科院分区：
文献类型：
--
作者：
Nakamura T;Mizuno S
自肝细胞生长因子（HGF）被发现是肝细胞的有丝分裂原以来，已经过去了25年多。HGF由基质细胞产生，通过其受体c - Met的酪氨酸磷酸化，刺激各种器官中的上皮细胞增殖、运动、形态发生和血管生成。在胎儿阶段，HGF中和或c - Met基因破坏会导致许多器官发育不全，这表明HGF信号对器官发育至关重要。内源性HGF是受损的肝脏、肾脏、肺等自我修复所必需的。此外，HGF通过抗凋亡和抗炎信号对上皮和非上皮器官（包括心脏和大脑）发挥保护作用。在器官疾病期间，血浆HGF水平显著升高，而在啮齿动物中注入抗HGF抗体则会加速组织破坏。因此，内源性HGF是减轻疾病所必需的，而HGF产生不足会导致器官衰竭。这就是为什么在病理条件下补充HGF会产生治疗效果的原因。此外，新出现的研究阐述了HGF在肿瘤转移过程中的关键作用，而拮抗HGF则会产生抗肿瘤效果。综上所述，基于HGF的分子，包括HGF变体、HGF片段和c - Met结合物，可作为再生或抗肿瘤药物。对HGF - c - Met系统的分子分析可以在基础生物学和临床医学之间架起桥梁。
It has been more than 25 years since HGF was discovered as a mitogen of hepatocytes. HGF is produced by stromal cells, and stimulates epithelial cell proliferation, motility, morphogenesis and angiogenesis in various organs via tyrosine phosphorylation of its receptor, c-Met. In fetal stages, HGF-neutralization, or c-Met gene destruction, leads to hypoplasia of many organs, indicating that HGF signals are essential for organ development. Endogenous HGF is required for self-repair of injured livers, kidneys, lungs and so on. In addition, HGF exerts protective effects on epithelial and non-epithelial organs (including the heart and brain) via anti-apoptotic and anti-inflammatory signals. During organ diseases, plasma HGF levels significantly increased, while anti-HGF antibody infusion accelerated tissue destruction in rodents. Thus, endogenous HGF is required for minimization of diseases, while insufficient production of HGF leads to organ failure. This is the reason why HGF supplementation produces therapeutic outcomes under pathological conditions. Moreover, emerging studies delineated key roles of HGF during tumor metastasis, while HGF-antagonism leads to anti-tumor outcomes. Taken together, HGF-based molecules, including HGF-variants, HGF-fragments and c-Met-binders are available as regenerative or anti-tumor drugs. Molecular analysis of the HGF-c-Met system could provide bridges between basic biology and clinical medicine.