教員業績データベース |
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論文種別 | 原著 |
言語種別 | 英語 |
査読の有無 | 査読あり |
表題 | Splenectomy attenuates murine liver fibrosis with hypersplenism stimulating hepatic accumulation of Ly-6Clo macrophages |
掲載誌名 | 正式名:Journal of hepatology 略 称:J Hepatol ISSNコード:1600-0641(Electronic)0168-8278(Linking) |
巻・号・頁 | 63(4),pp.905-16 |
著者・共著者 | Yada Akito, Iimuro Yuji, Uyama Naoki, Uda Yugo, Okada Toshihiro, Fujimoto Jiro |
発行年月 | 2015/10 |
概要 | BACKGROUND & AIMS:Splenectomy in cirrhotic patients has been reported to improve liver function; however the underlying mechanism remains obscure. In the present study, we investigated the mechanism using a murine model, which represents well the compensated liver cirrhosis.METHODS:C57BL/6 male mice were allowed to drink water including thioacetamide (TAA: 300mg/L) ad libitum for 32weeks. After splenectomy at 32weeks, mice were sacrificed on days onMETHODS:e, seven, and 28, respectively, while TAA-administration was continued. Perioperative changes in peripheral blood and liver tissues were analyzed.RESULTS:TAA treatment of mice for 32weeks reproducibly achieved advanced liver fibrosis with splenomegaly, thrombocytopenia, and leukocytopenia. After splenectomy, liver fibrosis was attenuated, and macrophages/monocytes were significantly increased in peripheral blood, as well as in the liver. Progenitor-like cells expressing CK-19, EpCAM, or CD-133 appeared in the liver after TAA treatment, and gradually disappeared after splenectomy. Macrophages/monocytes accumulated in the liver, most of which were negative for Ly-6C, were adjacent to the hepatic progenitor-like cells, and quantitative RT-PCR indicated increased canonical Wnt and decreased Notch signals. As a result, a significant amount of β-catenin accumulated in the progenitor-like cells. Moreover, relatively small Ki67-positive hepatic cells were significantly increased. Protein expression of MMP-9, to which Ly-6G-positive neutrophils contributed, was also increased in the liver after splenectomy.CONCLUSIONS:The hepatic accumulation of macrophages/monocytes, most of which are Ly-6C(lo), the reduction of fibrosis, and the gradual disappearance of hepatic progenitor-like cells possibly play significant roles in the tissue remodeling process in cirrhotic livers after splenectomy. |
DOI | 10.1016/j.jhep.2015.05.010 |
PMID | 26022691 |