Hepatocyte growth factor ameliorates acute graft-versus-host disease and promotes hematopoietic function
Hepatocyte growth factor ameliorates acute graft-versus-host disease and promotes hematopoietic function
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DOI：
10.1172/jci11808
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发表时间：
2001-06-01
影响因子：
15.9
通讯作者：
Iwasaki, T
中科院分区：
文献类型：
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作者：
Kuroiwa, T;Kakishita, E;Iwasaki, T
急性移植物抗宿主病(GVHD)是骨髓移植(BMT)的主要并发症，其特征是造血功能障碍、免疫抑制和皮肤、肝脏和肠道粘膜的组织损伤。肝细胞生长因子(HGF)最初被发现和克隆为一种强大的肝细胞有丝分裂原，可诱导多种上皮细胞的促有丝分裂和抗凋亡活性，并促进造血。在小鼠急性移植物抗宿主病(GVHD)模型上，我们将人肝细胞生长因子(HGF)基因多次导入小鼠骨骼肌，结果表明，HGF可抑制肠上皮细胞的凋亡和供体T细胞向肝脏的浸润，从而改善急性GVHD所致的肠病和肝损伤。HGF还能显著抑制肠道和肝脏中干扰素-γ和肿瘤坏死因子-α的表达，降低血清IL-12的水平。此外，供者细胞的骨髓外造血增加，存活率提高，提示ChAT-HGF可能有助于控制异基因骨髓移植后的急性移植物抗宿主病。
Acute graft-versus-host disease (GVHD) is a major complication of bone marrow transplantation (BMT) and is characterized by hematopoietic dysfunction, immunosuppression, and tissue injury in the skin, liver, and intestinal mucosa. Hepatocyte growth factor (HGF), originally identified and cloned as a potent mitogen for hepatocytes, induces mitogenic and antiapoptotic activity in various epithelial cells and promotes hematopoiesis. Working in a murine model of acute GVHD, we performed repeated transfection of the human HGF cDNA into skeletal muscle and showed that this treatment inhibited apoptosis of intestinal epithelial cells and donor T-cell infiltration into the liver, thereby ameliorating the enteropathy and liver injury caused by acute GVHD, HGF also markedly suppressed IFN-gamma and TNF-alpha expression in the intestine and liver and decreased the serum IL-12. Furthermore, extramedullary hematopoiesis by donor cells was increased, and the survival rate was improved, These results suggest chat HGF may be useful for controlling acute GVHD after allogeneic BMT.