Hepatocyte growth factor prevents lupus nephritis in a murine lupus model of chronic graft-versus-host disease.
Hepatocyte growth factor prevents lupus nephritis in a murine lupus model of chronic graft-versus-host disease.
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肝细胞生长因子在慢性移植物与宿主病的鼠狼疮模型中阻止狼疮肾炎。
DOI：
10.1186/ar2012
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发表时间：
2006
影响因子：
4.9
通讯作者：
Sano H
中科院分区：
文献类型：
--
作者：
Kuroiwa T;Iwasaki T;Imado T;Sekiguchi M;Fujimoto J;Sano H
在（C57 BL/6 × DBA/2）F1（BDF 1）小鼠中通过注射DBA/2小鼠脾细胞诱导慢性移植物抗宿主病（GVHD），表现为与系统性红斑狼疮（SLE）、原发性胆汁性肝硬化（PBC）和干燥综合征（SS）相关的组织病理学改变，如肾小球肾炎、淋巴细胞浸润到肝门静脉周围区和唾液腺。我们使用这种慢性GVHD模型来确定肝细胞生长因子（HGF）基因转染对狼疮的治疗效果。在慢性GVHD小鼠的臀肌中注射含有8 μg人HGF表达载体的HVJ脂质体（HGF-HVJ脂质体）或模拟载体（未处理的对照）。在12周内，每隔2周重复基因转移。HGF基因转染可有效地预防肾小球肾炎相关的蛋白尿和组织病理学改变。虽然未经处理的GVHD小鼠的肝脏和唾液腺切片显示出突出的PBC和SS样变化，但HGF基因转染减少了这些组织病理学变化。HGF基因转染显著降低了脾B细胞数量、宿主B细胞主要组织相容性复合物II类表达以及血清IgG和抗DNA抗体水平。肝细胞生长因子基因转染可显著降低脾、肝、肾组织中IL-4 mRNA的表达。体外实验表明，重组HGF可降低DBA/2CD 4 + T细胞表面CD 28的表达。此外，重组HGF在体外可显著抑制DBA/2 CD 4 + T细胞经辐射的BDF 1树突状细胞刺激产生IL-4。这些结果表明，HGF基因转染抑制T辅助细胞2免疫反应，并减少慢性GVHD小鼠的狼疮性肾炎，自身免疫性涎腺炎和胆管炎。HGF可能是治疗SLE、SS和PBC的新策略。
Chronic graft-versus-host disease (GVHD) induced in (C57BL/6 × DBA/2) F1 (BDF1) mice by the injection of DBA/2 mouse spleen cells represents histopathological changes associated with systemic lupus erythematosus (SLE), primary biliary cirrhosis (PBC) and Sjogren's syndrome (SS), as indicated by glomerulonephritis, lymphocyte infiltration into the periportal area of the liver and salivary glands. We determined the therapeutic effect of hepatocyte growth factor (HGF) gene transfection on lupus using this chronic GVHD model. Chronic GVHD mice were injected in the gluteal muscle with either HVJ liposomes containing 8 μg of the human HGF expression vector (HGF-HVJ liposomes) or mock vector (untreated control). Gene transfer was repeated at 2-week intervals during 12 weeks. HGF gene transfection effectively prevented the proteinuria and histopathological changes associated with glomerulonephritis. While liver and salivary gland sections from untreated GVHD mice showed prominent PBC- and SS-like changes, HGF gene transfection reduced these histopathological changes. HGF gene transfection greatly reduced the number of splenic B cells, host B cell major histocompatibility complex class II expression, and serum levels of IgG and anti-DNA antibodies. IL-4 mRNA expression in the spleen, liver, and kidneys was significantly decreased by HGF gene transfection. CD28 expression on DBA/2 CD4+ T cells was decreased by the addition of recombinant HGF in vitro. Furthermore, IL-4 production by DBA/2 CD4+ T cells stimulated by irradiated BDF1 dendritic cells was significantly inhibited by the addition of recombinant HGF in vitro. These results suggest that HGF gene transfection inhibited T helper 2 immune responses and reduced lupus nephritis, autoimmune sialoadenitis, and cholangitis in chronic GVHD mice. HGF may represent a novel strategy for the treatment of SLE, SS and PBC.
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影响因子：
20.3
作者：
Sato, K;Yamashita, N;Matsuyama, T
通讯作者：
Matsuyama, T
DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hawiger D;Inaba K;Dorsett Y;Guo M;Mahnke K;Rivera M;Ravetch JV;Steinman RM;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
15.9
作者：
Kuroiwa, T;Kakishita, E;Iwasaki, T
通讯作者：
Iwasaki, T
影响因子：
3.6
作者：
GARLISI, CG;PENNLINE, KJ;UMLAND, SP
通讯作者：
UMLAND, SP
影响因子：
4.4
作者：
Okamoto, I;Kohno, K;Kurimoto, M
通讯作者：
Kurimoto, M