Analysis of the role of angiogenesis and non-parenchymal cells during hepatic regeneration.

分析血管生成和非实质细胞在肝再生过程中的作用。

• 批准号: 17390375
• 负责人: FUJIMOTO Jiro
• 金额: $ 9.54万
• 依托单位: Hyogo College of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390375/
• 关键词: angiogenesis; HGF; NK4; VEGF; sFlt-1; liver regeneration; NK4

We investigated the influence of anti-angiogenesis for hepatic regeneration using HGF antagonist (NK4) and suppressor of VEGF receptor (sFlt-1). NK4 expressing adenoviral vector (Ad.NK4) or sFlt-1 expressing adenoviral vector (Ad.sFlt-1) were infected mice liver. Seventy percent hepatectomy was performed 48 hours after infection. LacZ expressing adenoviral vector (Ad.LacZ) was used as control. Expression of Nk4 or sFlt-1 reached maximum level 48 hours after infection (NK4: 300ng/ml, sFlt-1:350ng/ml) and sustained for 2 weeks. Remnant liver was removed at 12, 24, 36, 48, 72 and 120 hrs after partial hepatectomy, and hepatic regeneration was assessed. As a result, increase of remnant hepatic weight was significantly delayed in Ad.NK4 or Ad.sFlt-1 infected mice. Results of mitotic cells and BrdU index showed significant delay of hepatic regeneration in Ad.NK4 or Ad.sFlt-1 infected mice at 48 or 36 hours after hepatectomy. Immnuhistochemical staining of CD31 showed suppression of sinusoidal endothelial cells growth in Ad.NK4 infected mice. Ang-1, Ang-2, Tie-1, and Tie-2 are considered to be crucial in the process of maturation of vessels. Real time PCR showed suppression of mRNA of Ang-1, Ang-2, Tie-1, and Tie-2 with significant difference. These results suggested that hepatic regeneration after hepatectomy closely correlates with angiogenesis.

我们研究了使用 HGF 拮抗剂 (NK4) 和 VEGF 受体抑制剂 (sFlt-1) 抗血管生成对肝再生的影响。表达NK4的腺病毒载体(Ad.NK4)或表达sFlt-1的腺病毒载体(Ad.sFlt-1)感染小鼠肝脏。感染后 48 小时进行了 70% 的肝切除术。使用表达LacZ的腺病毒载体(Ad.LacZ)作为对照。 Nk4或sFlt-1的表达在感染后48小时达到最高水平（NK4：300ng/ml，sFlt-1：350ng/ml）并持续2周。部分肝切除后12、24、36、48、72和120小时取出残余肝脏，并评估肝再生。结果，Ad.NK4或Ad.sFlt-1感染的小鼠中残余肝重量的增加显着延迟。有丝分裂细胞和BrdU指数的结果显示，Ad.NK4或Ad.sFlt-1感染的小鼠在肝切除术后48或36小时肝再生显着延迟。 CD31 的免疫组织化学染色显示 Ad.NK4 感染小鼠的窦内皮细胞生长受到抑制。 Ang-1、Ang-2、Tie-1 和 Tie-2 被认为在血管成熟过程中至关重要。实时PCR显示Ang-1、Ang-2、Tie-1和Tie-2的mRNA受到显着抑制。这些结果表明肝切除术后的肝再生与血管生成密切相关。

项目成果

Oncostatin M inhibits proliferation of rat oval cells, OC15-5, inducing differentiation into hepatocytes.

• DOI: 10.1016/s0002-9440(10)62292-4
• 发表时间: 2005-03
• 期刊: The American journal of pathology
• 作者: A. Okaya;J. Kitanaka;N. Kitanaka;M. Satake;Yuna Kim;K. Terada;T. Sugiyama;M. Takemura;J. Fujimoto;N. Terada;A. Miyajima;T. Tsujimura

自然免疫と肝再生

先天免疫和肝再生

• 发表时间: 2006
• 期刊: 医学のあゆみ(別冊)消化器疾患 II. 肝・胆・膵 Ver.3
• 作者: Kuroiwa;T.;Iwasaki;T.;Imado;T.;Sekiguchi;M.;Fujimoto;J.;Sano;H.;飯室勇二
• 通讯作者: 飯室勇二

Hepatocyte growth factor prevents lupus nephritis in a murine lupus model of chronic graft-versus-host disease.

• DOI: 10.1186/ar2012
• 发表时间: 2006
• 期刊: Arthritis research & therapy
• 影响因子: 4.9
• 作者: Kuroiwa T;Iwasaki T;Imado T;Sekiguchi M;Fujimoto J;Sano H
• 通讯作者: Sano H

肝胆膵手術のための解剖.術式別看護手順がわかる実践消化器外科手術マニュアル

肝胆胰外科解剖学。实用胃肠外科手册，解释了每种外科手术的护理程序。

• 发表时间: 2006
• 作者: Oh;K.;limuro;Y.;Takeuchi;M.;Kaneda;Y.;Iwasaki;T.;Terada;N.;Matsumoto;T.;Nakanishi;K.;Fujimoto;J.;山中潤一
• 通讯作者: 山中潤一

肝硬変(その2).細胞増殖因子と再生医療

肝硬化（第二部​​分）.细胞生长因子与再生医学

• 发表时间: 2006
• 作者: Oh;K.;limuro;Y.;Takeuchi;M.;Kaneda;Y.;Iwasaki;T.;Terada;N.;Matsumoto;T.;Nakanishi;K.;Fujimoto;J.;山中潤一;鈴村和大
• 通讯作者: 鈴村和大