Activated hepatic stellate cell specific antibody that attenuates liver fibrosis: mechanism of action and therapeutic use

减轻肝纤维化的活化肝星细胞特异性抗体：作用机制和治疗用途

• 批准号: 24659367
• 负责人: YOKOSAKI Yasuyuki
• 金额: $ 2.41万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659367/
• 关键词: インテグリン; 線維症; 星細胞; TGF-β; 抗体医薬; 肝硬変; 肝線維化; 肺線維化; 阻害抗体; 筋線維芽細胞; モノクロナル抗体

We have previously generated an anti-integrin alpha8beta1 blocking antibody, which has been found to inhibit liver fibrosis in mouse models. In the present study, we aimed at the mechanism of the profibrotic activity of integrin alpha8beta1. We found that 1) alpha8beta1 activates TGF-beta that plays major roles in fibrosis, and 2) alpha8beta1 supports emergence of myofibroblast that is a constituent of fibrotic tissues. The activation was previously fond also in other integrins, but the myofibroblast induction was a novel finding.

我们以前已经产生了一种抗整合素α 8 β 1阻断抗体，已发现它可以抑制小鼠模型中的肝纤维化。在本研究中，我们的目的是整合素α 8 β 1的促纤维化活性的机制。我们发现1）α 8 β 1激活在纤维化中起主要作用的TGF-β，2）α 8 β 1支持肌成纤维细胞的出现，肌成纤维细胞是纤维化组织的组成部分。这种激活以前也见于其他整合素，但肌成纤维细胞诱导是一个新的发现。

项目成果

Deletion of Tetraspanin CD9 Diminishes Lymphangiogenesis in Vivo and in Vitro

• DOI: 10.1074/jbc.m112.424291
• 发表时间: 2013-01-25
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Iwasaki, Takeo;Takeda, Yoshito;Kumanogoh, Atsushi
• 通讯作者: Kumanogoh, Atsushi

Role ofα8β1 integrin in TGF-βactivation by lung fibroblasts

α8β1整合素在肺成纤维细胞TGF-β激活中的作用

• 发表时间: 2013
• 作者: Nick Mark;Chi Hung C;Yu-Hua Chow;Norihisa Nishimichi;Lynn Schnapp;Yasuyuki Yokosaki
• 通讯作者: Yasuyuki Yokosaki

A possible therapeutic agent for pulmonary fibrosis: antibody against integrin α8β1.

肺纤维化的可能治疗剂：整合素α8β1抗体。

• 发表时间: 2013
• 作者: Yokosaki Y;Nishimichi N;Kanno K;Senatani K;Yasui W.
• 通讯作者: Yasui W.

インテグリン治療開発フロンティア研究室

整合素疗法发展前沿实验室

Integrinα8β1 as a new therapeutic target for tissue fibrosis. American Thoracic Society

整合素α8β1作为组织纤维化的新治疗靶点。

• 发表时间: 2012
• 作者: Norihisa Nishimichi;Keishi Kanno;Neil C. Henderson;Dean Sheppard;Yasuyuki Yokosaki
• 通讯作者: Yasuyuki Yokosaki