TNFR1-mediated signaling is important to induce the improvement of liver fibrosis by bone marrow cell infusion.
TNFR1-mediated signaling is important to induce the improvement of liver fibrosis by bone marrow cell infusion.
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DOI：
10.1007/s00441-011-1236-0
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发表时间：
2011-10
影响因子：
3.6
通讯作者：
Sakaida, Isao
中科院分区：
文献类型：
--
作者：
Hisanaga, Takuro;Terai, Shuji;Iwamoto, Takuya;Takami, Taro;Yamamoto, Naoki;Murata, Tomoaki;Matsuyama, Toshifumi;Nishina, Hiroshi;Sakaida, Isao
研究了由肿瘤坏死因子受体1（TNFR 1）介导的TNF-α信号在四氯化碳（CCl 4）诱导的炎症和纤维化中的重要性，以及在损伤后肝再生中的重要性，包括通过骨髓细胞（BMC）输注开发作为肝修复模型的GFP/CCl 4模型。在TNFR 1通过拮抗剂给药或基因敲除抑制的小鼠中，CCl 4诱导的肝纤维化显著降低。在这些小鼠中，肝内巨噬细胞浸润和TGF-β1表达减少，星状细胞活性降低;然而，MMP-9的表达也降低。在这些小鼠中输注GFP阳性BMC（TNFR 1野生型，WT）后，纤维化增殖，包括宿主内源性肝内巨噬细胞浸润、TGF-β1表达和星状细胞活性显著增加。MMP-9表达无明显增加。在这项研究中，宿主中的TNFR 1对CCl 4诱导的肝毒性和纤维化具有促进作用，而TNFR 1敲除小鼠中的BMC输注增强了宿主源性肝内炎症和纤维化增殖。这些发现不同于WT受体小鼠中的那些，其中先前报道了BMC输注改善炎症和纤维化。TNFR 1介导的信号传导可能在骨髓细胞输注诱导肝纤维化改善中起重要作用。
The importance of TNF-α signals mediated by tumor necrosis factor receptor type 1 (TNFR1) in inflammation and fibrosis induced by carbon tetrachloride (CCl4), and in post-injury liver regeneration including a GFP/CCl4 model developed as a liver repair model by bone marrow cell (BMC) infusion, was investigated. In mice in which TNFR1 was suppressed by antagonist administration or by knockout, liver fibrosis induced by CCl4 was significantly decreased. In these mice, intrahepatic macrophage infiltration and TGF-β1 expression were reduced and stellate cell activity was decreased; however, expression of MMP-9 was also decreased. With GFP-positive BMC (TNFR1 wild-type, WT) infusion in these mice, fibrosis proliferation, including host endogenous intrahepatic macrophage infiltration, TGF-β1 expression and stellate cell activity, increased significantly. There was no significant increase of MMP-9 expression. In this study, TNFR1 in hosts had a promoting effect on CCl4-induced hepatotoxicity and fibrosis, whereas BMC infusion in TNFR1 knockout mice enhanced host-derived intrahepatic inflammation and fibrosis proliferation. These findings differed from those in WT recipient mice, in which improvement in inflammation and fibrosis with BMC infusion had previously been reported. TNFR1-mediated signaling might be important to induce the improvement of liver fibrosis by bone marrow cell infusion.
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