Sanada Fumihiro, Fujikawa Tatsuya, Shibata Kana, Taniyama Yoshiaki, Rakugi Hiromi, Morishita Ryuichi
Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Department of Geriatric and General Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Ann Vasc Dis. 2020 Jun 25;13(2):109-115. doi: 10.3400/avd.ra.20-00035.
Hepatocyte growth factor (HGF) is secreted from stromal and mesenchymal cells, and its receptor cMet is expressed on various types of cells such as smooth muscle cells, fibroblast, and endothelial cells. HGF stimulates epithelial and endothelial cell proliferation, motility, and morphogenesis in a paracrine and autocrine manner, organizing multistep of angiogenesis in many organs. In addition, HGF is recognized as a potent anti-inflammatory and anti-fibrotic growth factor, which has been proved in several animal studies, including neointimal hyperplasia and acute myocardial infarction model in rodent. Thus, as compared to other angiogenic growth factors, HGF exerts multiple effects on ischemic tissues, accompanied by the regression of tissue inflammation and fibrosis. These data suggest the therapeutic potential of the HGF for peripheral artery disease as it being accompanied with chronic tissue inflammation and fibrosis. In the present narrative review, the pleiotropic action of the HGF that differentiates it from other angiogenic growth factors is discussed first, and later, outcomes of the human clinical study with gene therapy are overviewed.
肝细胞生长因子（HGF）由基质细胞和间充质细胞分泌，其受体cMet在多种类型的细胞上表达，如平滑肌细胞、成纤维细胞和内皮细胞。HGF以旁分泌和自分泌方式刺激上皮细胞和内皮细胞的增殖、迁移和形态发生，在许多器官中组织多步骤的血管生成。此外，HGF被认为是一种有效的抗炎和抗纤维化生长因子，这已在多项动物研究中得到证实，包括啮齿动物的内膜增生和急性心肌梗死模型。因此，与其他血管生成生长因子相比，HGF对缺血组织具有多种作用，同时伴有组织炎症和纤维化的消退。这些数据表明HGF在治疗伴有慢性组织炎症和纤维化的外周动脉疾病方面具有潜在的治疗价值。在本叙述性综述中，首先讨论了HGF与其他血管生成生长因子不同的多效性作用，随后概述了基因治疗的人体临床研究结果。
