Wu M-H, Yokozeki H, Takagawa S, Yamamoto T, Satoh T, Kaneda Y, Katayama I, Nishioka K
Department of Dermatology and Immunodermatology, Tokyo Medical and Dental University, Graduate School, Tokyo, Japan.
Gene Ther. 2004 Jan;11(2):170-80. doi: 10.1038/sj.gt.3302165.
Systemic sclerosis (SSc) is a connective tissue disorder with an unknown etiology. There are currently no effective therapies for SSc. (In this study, working with a bleomycin(BLM)-induced scleroderma model mice, we performed two transfections of human hepatocyte growth factor (HGF) cDNA into the skeletal muscle and showed that this treatment not only helped to prevent the dermal sclerosis simultaneously injected BLM but also improved the symptoms of dermal sclerosis induced by BLM 4 weeks previously.) RT-PCR, ELISA and an immunohistochemical analysis revealed that both mRNA and protein of human HGF as well as murine HGF were enhanced in the skin, lung, muscle and the serum after two transfections of human HGF cDNA. These analyses also revealed that this treatment significantly reduced both the expression of the TGF-beta1 mRNA and the production of TGF-beta1 on macrophage-like cells that infiltrated the dermis and the fibroblastic cells in BLM-induced scleroderma. Furthermore, HGF-gene transfection both prevented and ameliorated the symptoms of not only dermal sclerosis but also of lung fibrosis induced by a subcutaneous BLM injection. These results indicated that gene therapy by the transfection of the human HGF cDNA may thus be a useful therapy for SSc and lung fibrosis involved with SSc.
系统性硬化症（SSc）是一种病因不明的结缔组织疾病。目前尚无针对SSc的有效治疗方法。（在本研究中，我们使用博来霉素（BLM）诱导的硬皮病模型小鼠，将人肝细胞生长因子（HGF）cDNA转染至骨骼肌两次，结果显示该治疗不仅有助于预防同时注射BLM所致的皮肤硬化，还能改善4周前由BLM诱导的皮肤硬化症状。）逆转录聚合酶链反应（RT-PCR）、酶联免疫吸附测定（ELISA）和免疫组织化学分析显示，转染人HGF cDNA两次后，人HGF以及小鼠HGF的mRNA和蛋白在皮肤、肺、肌肉和血清中均有所增加。这些分析还显示，该治疗显著降低了BLM诱导的硬皮病中浸润真皮的巨噬细胞样细胞和成纤维细胞上TGF-β1 mRNA的表达以及TGF-β1的产生。此外，HGF基因转染不仅预防和改善了皮肤硬化症状，还改善了皮下注射BLM所致的肺纤维化症状。这些结果表明，转染人HGF cDNA的基因治疗可能是治疗SSc以及与SSc相关的肺纤维化的有效方法。
