Lack of tumor necrosis factor receptor type 1 inhibits liver fibrosis induced by carbon tetrachloride in mice
Lack of tumor necrosis factor receptor type 1 inhibits liver fibrosis induced by carbon tetrachloride in mice
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DOI：
10.1016/j.cyto.2004.11.001
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发表时间：
2005-03-07
期刊：
影响因子：
3.8
通讯作者：
Seishima, M
中科院分区：
文献类型：
--
作者：
Sudo, K;Yamada, Y;Seishima, M
慢性肝损伤引起肝再生，导致纤维化。促炎细胞因子肿瘤坏死因子（TNF）参与了许多急性和慢性肝病的发病机制。TNF具有多种功能，但其在肝纤维化中的作用尚未阐明。慢性重复注射CCl_4诱导小鼠肝纤维化。我们研究了通过TNF受体的信号传导是否对这一过程至关重要，使用缺乏TNF受体（TNFR）1型或TNFR 2型的小鼠来确定TNFR信号在肝纤维化中的病理生理作用。慢性CCl 4暴露引起的肝纤维化是TNF依赖性的;在野生型（WT）和TNFR-2敲除（KO）小鼠中观察到组织学纤维化，但在TNFR-1 KO小鼠中未观察到。此外，在TNFR-1 KO小鼠中观察到前胶原和TGF-β合成的显著减少，与WT和TNFR-2 KO小鼠相比，TNFR-1 KO小鼠也几乎没有可检测到的NF-κ B、STAT 3和AP 1结合，并且肝脏白细胞介素-6（IL-6）mRNA水平降低。总之，我们的研究结果表明，NF-κ B B，STAT 3，和API结合的信号转导通过TNFR-I在肝纤维化形成中起着重要作用的可能性。(c)2005爱思唯尔有限公司保留所有权利。
Chronic liver injury causes liver regeneration, resulting in fibrosis. The proinflammatory cytokine tumor necrosis factor (TNF) is involved in the pathogenesis of many acute and chronic liver diseases. TNF has pleiotropic functions, but its role in liver fibrosis has not been clarified. Chronic repeated injection Of CCl4 induces liver fibrosis in mice. We examined whether signaling through TNF receptors was critical for this process, using mice lacking either TNF receptor (TNFR) type 1 or TNFR type 2 to define the pathophysiologic role of TNFR signals in liver fibrosis. Liver fibrosis caused by chronic CCl4 exposure was TNF-dependent; histological fibrosis was seen in wild-type (WT) and TNFR-2 knockout (KO) mice, but not in TNFR-1 KO mice. Furthermore, a marked reduction in procollagen and TGF-beta synthesis was observed in TNFR-1 KO mice, which also had little detectable NF-kappa B, STAT3, and AP1 binding, and reduced levels of liver interleukin-6 (IL-6) mRNA compared to WT and TNFR-2 KO mice. In conclusion, our results indicate the possibility that NF-kappa B, STAT3, and API binding by signals transduced through TNFR-I plays an important role in liver fibrosis formation. (c) 2005 Elsevier Ltd. All rights reserved.