Nakanishi Kuniaki, Uenoyama Maki, Tomita Naruya, Morishita Ryuichi, Kaneda Yasufumi, Ogihara Toshio, Matsumoto Kunio, Nakamura Toshikazu, Maruta Akie, Matsuyama Shigeo, Kawai Toshiaki, Aurues Takashi, Hayashi Takuya, Ikeda Tomosumi
Division of Environmental Medicine, National Defense Medical College, Tokorozawa, Japan.
Am J Pathol. 2002 Nov;161(5):1761-72. doi: 10.1016/S0002-9440(10)64453-7.
Hepatocyte growth factor (HGF) regulates cell growth, cell motility, and morphogenesis in various types of cells, including epithelial and endothelial cells, indicating that it probably promotes epithelial repair and neovascularization during wound healing. To better understand the effects of HGF on wound healing, we performed human HGF-gene transfer into skin wounds in rats. The rat HGF mRNA levels, and human and rat HGF protein concentrations in the wounds in HGF gene-transfer rats were significantly elevated at 3 days, 3 to 14 days, and 3 and 14 days after gene transfer, respectively. An expression of human HGF mRNA and protein was revealed in squamous cells in the epidermis, in endothelial cells and smooth muscle cells in blood vessels, and in fibroblasts in granulation tissues at 3, 7, and 14 days after gene transfer in HGF gene-transfer rats. The wound lesion area in HGF gene-transfer rats was significantly less than that in control rats from 3 to 7 days after gene transfer. The re-epithelialization rate, microvessel counts in granulation tissues, proliferating cell nuclear antigen index of fibroblasts in granulation tissues, and the proliferating cell nuclear antigen index in the epidermis of HGF gene-transfer rats were significantly increased at 3 and 7 days after gene transfer. Semiquantitative reverse transcriptase-polymerase chain reaction revealed that the expression levels of transforming growth factor-beta1 and Colalpha2(I) mRNAs in the wounds of HGF gene-transfer rats were significantly decreased at 7 and 14 days, respectively. The hydroxyproline concentration in the wound was significantly less in HGF gene-transfer rats than in control rats at 3 days after gene transfer. These results suggest that HGF gene transfer into a skin wound may aid re-epithelialization and neovascularization in the early phase of wound healing, and that HGF may play a role in modulating cutaneous wound healing.
肝细胞生长因子（HGF）可调节多种类型细胞的细胞生长、细胞运动及形态发生，这些细胞包括上皮细胞和内皮细胞，这表明它可能在伤口愈合过程中促进上皮修复和新血管形成。为了更好地理解HGF对伤口愈合的影响，我们将人HGF基因导入大鼠皮肤伤口。在基因转移后3天、3至14天以及3天和14天，HGF基因转移大鼠伤口中的大鼠HGF mRNA水平以及人和大鼠HGF蛋白浓度分别显著升高。在HGF基因转移大鼠基因转移后3天、7天和14天，在表皮的鳞状细胞、血管内皮细胞和平滑肌细胞以及肉芽组织中的成纤维细胞中均检测到了人HGF mRNA和蛋白的表达。在基因转移后3至7天，HGF基因转移大鼠的伤口病变面积显著小于对照大鼠。在基因转移后3天和7天，HGF基因转移大鼠的再上皮化率、肉芽组织中的微血管计数、肉芽组织中成纤维细胞的增殖细胞核抗原指数以及表皮中的增殖细胞核抗原指数均显著增加。半定量逆转录聚合酶链反应显示，在基因转移后7天和14天，HGF基因转移大鼠伤口中转化生长因子-β1和Colα2（I）mRNA的表达水平分别显著降低。在基因转移后3天，HGF基因转移大鼠伤口中的羟脯氨酸浓度显著低于对照大鼠。这些结果表明，将HGF基因导入皮肤伤口可能有助于伤口愈合早期的再上皮化和新血管形成，并且HGF可能在调节皮肤伤口愈合中发挥作用。
