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厦门大学Science医学：发布再生医学重大突破

2016-08-20 生物通/何嫱 生物通/何嫱

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吞服一颗药丸来修复一个器官有可能最终会成为现实。避开传统的支架、材料和基于细胞的再生医学策略，来自厦门大学、北京大学的研究人员找到了一种小分子能够特异地靶向Hippo信号通路中的关键信号分子激酶MST1 和MST2来促进组织细胞修复与再生。这一重要的研究成果发布在8月17日的《科学转化医学》（Science Translational Medicine）杂志上。厦门大学生命科学学院的周大旺（Daw



吞服一颗药丸来修复一个器官有可能最终会成为现实。避开传统的支架、材料和基于细胞的再生医学策略，来自厦门大学、北京大学的研究人员找到了一种小分子能够特异地靶向Hippo信号通路中的关键信号分子激酶MST1 和MST2来促进组织细胞修复与再生。这一重要的研究成果发布在8月17日的《科学转化医学》（Science Translational Medicine）杂志上。

厦门大学生命科学学院的周大旺（Dawang Zhou）教授、邓贤明（Xianming Deng）教授，以及北京大学医学部的云彩红（Cai-Hong Yun）教授是这篇论文的共同通讯作者。邓贤明教授的主要研究领域是化学生物学和药物化学。

周大旺教授长期从事Hippo信号通路在免疫细胞与组织稳态维持的调节机制的研究。2015年2月，周大旺教授以及厦门大学生命科学学院的陈兰芬教授领导研究人员证实，Yap整合Hippo信号及未折叠蛋白反应（UPR）阻止了肝脏过度生长及肿瘤发生。这一重要的研究发现发表在Nature Communications杂志上。

云彩红教授主要从事结构生物学和结构药理学/三维结构指导理性药物设计研究，研究兴趣集中于肿瘤发病机理、耐药机理和靶向性抗癌药物的研发。今年5月，云彩红教授Cell杂志上发表文章，对2010年波恩莱茵弗里德里希•威廉大学Michael Famulok课题组发表在Cell杂志上的一项研究提出了质疑，指出缺乏证据表明CYTH2/ARNO是EGFR的直接胞内激活因子。

组织修复与再生医学可解决采用功能组织替代受损组织这一重要的医学需求。然而当前大多数的再生医学策略都将焦点放在传送生物材料和细胞上，尚未深入挖掘具有良好特异性和安全性的药物诱导再生的潜力。

Hippo信号通过抑制细胞增殖和促进凋亡，是器官大小和再生的一个重要的调控因子。哺乳动物Hippo的直系同源物：激酶MST1和MST2 (MST1/2)是这一信号通路的中心元件，因此是药物诱导组织再生的一个有力的候选靶点。


在这篇文章中，研究人员报告称采用基于酶联免疫吸附试验的高通量生物化学分析，发现了一种可逆的选择性MST1/2抑制剂：4-((5,10-dimethyl-6-oxo-6,10-dihydro-5H-pyrimido[5,4-b]thieno[3,2-e][1,4]diazepin-2-yl)amino)benzenesulfonamide (XMU-MP-1)。共晶结构和结构-活性关系证实XMU-MP-1击中MST1/2。XMU-MP-1阻断了MST1/2激酶活性，由此激活了下游效应器Yes相关蛋白(Yes-associated protein，YAP)，促进了细胞生长。

XMU-MP-1在体内显示极好的药物代谢动力学，以1-3 mg/kg的剂量腹腔内注射XMU-MP-1，研究人员证实在急性和慢性肝损伤小鼠模型中均能促进小鼠肠修复以及肝修复和再生。相比于运载工具处理对照组，在Fah缺陷小鼠模型中XMU-MP-1处理显示显著更大的人类肝细胞增殖速率，表明XMU-MP-1处理可能促进了人类肝脏再生。

因此，药物调节MST1/2激酶活性提供了一种增强组织修复和再生的新方法，XMU-MP-1可作为开发靶向再生疗法的首个先导药物。

原始出处

Fuqin Fan1,2,*, Zhixiang He1,2,*, Lu-Lu Kong3,*, Qinghua Chen1,2,*, Quan Yuan4,*, Shihao Zhang1,2, Jinjin Ye1,2, Hao Liu1,2, Xiufeng Sun1,2, Jing Geng1,2, Lunzhi Yuan4, Lixin Hong1,2, Chen Xiao1,2, Weiji Zhang1,2, Xihuan Sun1,2, Yunzhan Li1,2, Ping Wang1,2, Lihong Huang1,2, Xinrui Wu1,2, Zhiliang Ji1,2, Qiao Wu1,2, Ning-Shao Xia4, Nathanael S. Gray5, Lanfen Chen1,2, Cai-Hong Yun3,†, Xianming Deng1,2,† and Dawang Zhou1,2,†.Pharmacological targeting of kinases MST1 and MST2 augments tissue repair and regeneration.Science.2016

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    2017-04-12 xqptu

    #厦门#

    0

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    2016-09-17 doctorJiangchao

    继续学习

    0

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likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160821/IMG57B9667502B1F9208.jpg, createdBy=7a291940143, createdName=茶马古道, createdTime=Mon Aug 22 23:20:00 CST 2016, time=2016-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=102211, encodeId=f6a31022117f, content=很好的研究！, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160821/IMG57B9667502B1F9208.jpg, createdBy=7a291940143, createdName=茶马古道, createdTime=Mon Aug 22 10:33:00 CST 2016, time=2016-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1375319, encodeId=4e2213e5319de, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, 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objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/12/17/3872cad7a53dc9dcbd08202fb6313cf4.jpg, createdBy=2cb71609450, createdName=KO229256262, createdTime=Sat Aug 20 21:37:00 CST 2016, time=2016-08-20, status=1, ipAttribution=)]
    2016-09-17 doctorJiangchao

    继续关注

    0

  4. 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objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/12/17/3872cad7a53dc9dcbd08202fb6313cf4.jpg, createdBy=2cb71609450, createdName=KO229256262, createdTime=Sat Aug 20 21:37:00 CST 2016, time=2016-08-20, status=1, ipAttribution=)]
    2016-08-26 李东泽

    这篇资讯写的真好，带给我们新知识，启发新思维，不论是科研还是临床工作都有很大的帮助。。。

    0

  5. 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objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/12/17/3872cad7a53dc9dcbd08202fb6313cf4.jpg, createdBy=2cb71609450, createdName=KO229256262, createdTime=Sat Aug 20 21:37:00 CST 2016, time=2016-08-20, status=1, ipAttribution=)]
    2016-08-25 李东泽

    这些研究很喜欢，觉得好好玩，可以增加见识。。

    0

  6. 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beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Mon Aug 22 01:56:00 CST 2016, time=2016-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=101919, encodeId=7a1110191985, content=了解了！！！！！, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160817/IMG57B3C3F6DC2FD8753.jpg, createdBy=81321934679, createdName=1e0d99ddm02(暂无匿称), createdTime=Sun Aug 21 13:00:00 CST 2016, time=2016-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=101805, encodeId=409910180543, content=这下玩的真猛, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/12/17/3872cad7a53dc9dcbd08202fb6313cf4.jpg, createdBy=2cb71609450, createdName=KO229256262, createdTime=Sat Aug 20 21:37:00 CST 2016, time=2016-08-20, status=1, ipAttribution=)]
    2016-08-22 茶马古道

    学习了！不错！

    0

  7. 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likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160821/IMG57B9667502B1F9208.jpg, createdBy=7a291940143, createdName=茶马古道, createdTime=Mon Aug 22 23:20:00 CST 2016, time=2016-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=102211, encodeId=f6a31022117f, content=很好的研究！, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160821/IMG57B9667502B1F9208.jpg, createdBy=7a291940143, createdName=茶马古道, createdTime=Mon Aug 22 10:33:00 CST 2016, time=2016-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1375319, encodeId=4e2213e5319de, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Mon Aug 22 01:56:00 CST 2016, time=2016-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=101919, encodeId=7a1110191985, content=了解了！！！！！, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160817/IMG57B3C3F6DC2FD8753.jpg, createdBy=81321934679, createdName=1e0d99ddm02(暂无匿称), createdTime=Sun Aug 21 13:00:00 CST 2016, time=2016-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=101805, encodeId=409910180543, content=这下玩的真猛, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/12/17/3872cad7a53dc9dcbd08202fb6313cf4.jpg, createdBy=2cb71609450, createdName=KO229256262, createdTime=Sat Aug 20 21:37:00 CST 2016, time=2016-08-20, status=1, ipAttribution=)]
    2016-08-22 茶马古道

    很好的研究！

    0

  8. 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likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160821/IMG57B9667502B1F9208.jpg, createdBy=7a291940143, createdName=茶马古道, createdTime=Mon Aug 22 23:20:00 CST 2016, time=2016-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=102211, encodeId=f6a31022117f, content=很好的研究！, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160821/IMG57B9667502B1F9208.jpg, createdBy=7a291940143, createdName=茶马古道, createdTime=Mon Aug 22 10:33:00 CST 2016, time=2016-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1375319, encodeId=4e2213e5319de, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, 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objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/12/17/3872cad7a53dc9dcbd08202fb6313cf4.jpg, createdBy=2cb71609450, createdName=KO229256262, createdTime=Sat Aug 20 21:37:00 CST 2016, time=2016-08-20, status=1, ipAttribution=)]
    2016-08-22 jichang

    #SCIE#

    0

  9. 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objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/12/17/3872cad7a53dc9dcbd08202fb6313cf4.jpg, createdBy=2cb71609450, createdName=KO229256262, createdTime=Sat Aug 20 21:37:00 CST 2016, time=2016-08-20, status=1, ipAttribution=)]
    2016-08-21 1e0d99ddm02(暂无匿称)

    了解了！！！！！

    0

  10. [GetPortalCommentsPageByObjectIdResponse(id=1660652, encodeId=cb08166065250, content=<a href='/topic/show?id=803c3e216cf' target=_blank style='color:#2F92EE;'>#厦门#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=37216, encryptionId=803c3e216cf, topicName=厦门)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=552a25130440, createdName=xqptu, createdTime=Wed Apr 12 05:56:00 CST 2017, time=2017-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=129555, encodeId=cc2e1295557d, content=继续学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Sat Sep 17 14:10:00 CST 2016, time=2016-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=129556, encodeId=1d46129556ff, content=继续关注, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzfPkmqRTH5rHib5mcib8Wb3QdXjhfOK1UubQL2lictjJFdFJ6Lc3cnnCOSWqxXZ4Kk6y5GdzDoy764R/0, createdBy=156e1644785, createdName=doctorJiangchao, createdTime=Sat Sep 17 14:10:00 CST 2016, time=2016-09-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=104263, encodeId=d96e10426398, content=这篇资讯写的真好，带给我们新知识，启发新思维，不论是科研还是临床工作都有很大的帮助。。。, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzUn81b5CF5ibVPib8jWI92iciaxmqGHlwruOnK4SVZykd4iahqo1hicklIibyZoxm55X7EM8BW9eX1h1hQ2/0, createdBy=8aa81937526, createdName=李东泽, createdTime=Fri Aug 26 10:47:00 CST 2016, time=2016-08-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=103748, encodeId=fe90103e48e0, content=这些研究很喜欢，觉得好好玩，可以增加见识。。, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzUn81b5CF5ibVPib8jWI92iciaxmqGHlwruOnK4SVZykd4iahqo1hicklIibyZoxm55X7EM8BW9eX1h1hQ2/0, createdBy=8aa81937526, createdName=李东泽, createdTime=Thu Aug 25 18:35:00 CST 2016, time=2016-08-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=102424, encodeId=faf01024241e, content=学习了！不错！, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160821/IMG57B9667502B1F9208.jpg, createdBy=7a291940143, createdName=茶马古道, createdTime=Mon Aug 22 23:20:00 CST 2016, time=2016-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=102211, encodeId=f6a31022117f, content=很好的研究！, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160821/IMG57B9667502B1F9208.jpg, createdBy=7a291940143, createdName=茶马古道, createdTime=Mon Aug 22 10:33:00 CST 2016, time=2016-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1375319, encodeId=4e2213e5319de, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=20, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Mon Aug 22 01:56:00 CST 2016, time=2016-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=101919, encodeId=7a1110191985, content=了解了！！！！！, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20160817/IMG57B3C3F6DC2FD8753.jpg, createdBy=81321934679, createdName=1e0d99ddm02(暂无匿称), createdTime=Sun Aug 21 13:00:00 CST 2016, time=2016-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=101805, encodeId=409910180543, content=这下玩的真猛, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/12/17/3872cad7a53dc9dcbd08202fb6313cf4.jpg, createdBy=2cb71609450, createdName=KO229256262, createdTime=Sat Aug 20 21:37:00 CST 2016, time=2016-08-20, status=1, ipAttribution=)]
    2016-08-20 KO229256262

    这下玩的真猛

    0

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