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Circulation.：抑制Tspan12改善血管增生性视网膜病变

2017-04-04 MedSci MedSci原创

Tspan12血管增生视网膜病变
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抗血管生成物质是治疗血管增生性疾病的重要部分。然而，需要持续治疗、治疗无应答和副作用的风险限制了其应用。虽然已经显示Tspan12可以调节视网膜血管发育，但是尚未报道Tspan12是否参与新生血管形成及治疗血管增生性疾病。近日一篇《抗体介导的抑制Tspan12通过抑制β-连环蛋白信号来改善血管增生性视网膜病变》研究文章发表于著名血管杂志Circulation。研究使用两种视网膜新血管病变模型：两种

抗血管生成物质是治疗血管增生性疾病的重要部分。然而，需要持续治疗、治疗无应答和副作用的风险限制了其应用。虽然已经显示Tspan12可以调节视网膜血管发育，但是尚未报道Tspan12是否参与新生血管形成及治疗血管增生性疾病。

近日一篇《抗体介导的抑制Tspan12通过抑制β-连环蛋白信号来改善血管增生性视网膜病变》研究文章发表于著名血管杂志Circulation。研究使用两种视网膜新血管病变模型：两种氧诱导的视网膜病变（OIR）的小鼠模型和极低密度脂蛋白受体（VLDLR）敲除（KO）的小鼠模型分析Tspan /β-连环蛋白信号通路。筛选人组合抗体文库用于开发针对Tspan12的高亲和力抗体。在OIR和VLDLR KO小鼠模型中对新开发的针对血管内皮细胞的抗体的治疗效果进行体内/外检测。

新开发的Tspan12抗体显着抑制内皮细胞迁移和微管形成。机制研究证实此抗体抑制Tspan12和Frizzled-4之间的相互作用，有效调节血管内皮细胞中的β-连环蛋白水平及其靶基因。给予OIR和VLDLR小鼠增殖性视网膜病变模型急性和慢性刺激可激活Tspan12 /β-连环蛋白信号。给予在两种模型玻璃体内应用抗体都显示出显着的治疗效果，而不会对视网膜功能引起负面作用。此外，玻璃体内联合使用抗体与血管内皮生长因子（VEGF）抑制剂Aflibercept，显示出比每种单一疗法治疗功效都显着强大的效果。使用Tspan12阻断抗体联合治疗来降低抗VEGF剂量，从而降低长期脱靶效应的风险。

Tspan12 /β-连环蛋白信号传导对血管增生性疾病的发生发展至关重要。新开发的抗Tspan12抗体在血管增生性视网膜病变中具有治疗作用，并且可以增强现有的抗VEGF剂的效应。

原始出处：

Bucher F， Zhang D，et al.Antibody-Mediated Inhibition of Tspan12 Ameliorates Vasoproliferative Retinopathy Through Suppression of β-Catenin Signaling. Circulation. 2017 Mar 29. pii： CIRCULATIONAHA.116.025604.

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    2017-12-16 gostraight

    #SpA#

    0

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    2017-07-17 ms7514935887898259

    #增生性#

    0

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    2017-04-12 大爰

    学习了不错！！

    0

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    2017-04-06 虈亣靌

    优质资源，共同分享

    0

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    2017-04-06 cqykthl

    抗血管生成还是需要联合。

    0

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    2017-04-05 zutt

    #视网膜#

    0

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    2017-04-05 zhanfl

    #视网膜病变#

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1989391, encodeId=d78a198939139, content=<a href='/topic/show?id=7033165e692' target=_blank style='color:#2F92EE;'>#SpA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16576, encryptionId=7033165e692, topicName=SpA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=db5b227, createdName=gostraight, createdTime=Sat Dec 16 16:00:00 CST 2017, time=2017-12-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1757291, encodeId=25eb1e572916f, content=<a href='/topic/show?id=2f354231613' target=_blank style='color:#2F92EE;'>#增生性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=42316, encryptionId=2f354231613, topicName=增生性)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1f7c37300907, createdName=ms7514935887898259, createdTime=Mon Jul 17 23:00:00 CST 2017, time=2017-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=186800, encodeId=362218680035, content=学习了不错！！, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200816/e4675a86ea694f12b82202b320dc2654/12f6b900498349e994ce8f516a584d6a.jpg, createdBy=09431951290, createdName=大爰, createdTime=Wed Apr 12 07:44:03 CST 2017, time=2017-04-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=185601, encodeId=075618560176, content=优质资源，共同分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mONcle9pic3zMoyicyo6ia9f4IuLQAwZoxD6Hx4ibd5CMcOCYhStY6oDibbKK6O2X8iaicldO5ib8j1iapOIobIKCGiczU2A/0, createdBy=56251941490, createdName=虈亣靌, createdTime=Thu Apr 06 19:01:41 CST 2017, time=2017-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=185499, encodeId=b1111854990f, content=抗血管生成还是需要联合。, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NdicLmdJEK9VoiaDianY6fzHNN9iaGv80m39pMHU3eSnNN0kn1o0rdQ7Bz2f03Qibcf1ia7rKvxIt4UVlErF2d4gCmDC5/0, createdBy=98e31740255, createdName=cqykthl, createdTime=Thu Apr 06 08:25:29 CST 2017, time=2017-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1269858, encodeId=c5ab1269858ef, content=<a href='/topic/show?id=979690e33bd' target=_blank style='color:#2F92EE;'>#视网膜#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=90733, encryptionId=979690e33bd, topicName=视网膜)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=742793, createdName=zutt, createdTime=Wed Apr 05 15:00:00 CST 2017, time=2017-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1413878, encodeId=4b9014138e898, content=<a href='/topic/show?id=27b290e82f4' target=_blank style='color:#2F92EE;'>#视网膜病变#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=90782, encryptionId=27b290e82f4, topicName=视网膜病变)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f7143034078, createdName=zhanfl, createdTime=Wed Apr 05 15:00:00 CST 2017, time=2017-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=185228, encodeId=1b5118522875, content=学习了很有用, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib3IzoRn621JdKCFUI4XvNELcibocrAVU6aUzEVDSaf3rYH08PUYUiagGqxAEhj8g9WqqNvD1CupIpCrmnR2OrqHZh/0, createdBy=7f181365728, createdName=飛歌, createdTime=Wed Apr 05 01:19:53 CST 2017, time=2017-04-05, status=1, ipAttribution=)]
    2017-04-05 飛歌

    学习了很有用

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