Hepatocyte growth factor both prevents and ameliorates the symptoms of dermal sclerosis in a mouse model of scleroderma
Hepatocyte growth factor both prevents and ameliorates the symptoms of dermal sclerosis in a mouse model of scleroderma
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DOI：
10.1038/sj.gt.3302165
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发表时间：
2004
期刊：
影响因子：
5.1
通讯作者：
Minghua Wu;H. Yokozeki;S. Takagawa;Toshiyuki Yamamoto;Takahiro Satoh;Y. Kaneda;Ichiro Katayama;K. Nishioka
中科院分区：
文献类型：
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作者：
Minghua Wu;H. Yokozeki;S. Takagawa;Toshiyuki Yamamoto;Takahiro Satoh;Y. Kaneda;Ichiro Katayama;K. Nishioka
系统性硬化症（SSc）是一种病因不明的结缔组织疾病。目前还没有有效的治疗SSc的方法。(In本研究用博莱霉素（BLM）诱导的硬皮病模型小鼠，我们进行了两次人肝细胞生长因子（HGF）cDNA转染到骨骼肌中，并且表明这种治疗不仅有助于预防同时注射BLM的皮肤硬化，而且还改善了4周前由BLM诱导的皮肤硬化的症状。RT-PCR、ELISA和免疫组化分析表明，两次转染人HGF cDNA后，人HGF和小鼠HGF在皮肤、肺、肌肉和血清中的mRNA和蛋白表达均增强。这些分析还显示，该处理显著降低了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-β 1 mRNA的表达和TGF-β 1的产生。此外，HGF基因转染不仅预防和改善了皮肤硬化的症状，而且还预防和改善了由皮下BLM注射诱导的肺纤维化的症状。这些结果表明，通过转染人HGF cDNA的基因治疗可能因此是一个有用的治疗SSc和肺纤维化涉及SSc。
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-β1 mRNA and the production of TGF-β1 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.