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Sci Rep：抑制Wnt/β-catenin可抑制肺间充质干细胞肌纤维母细胞分化和肺纤维化

2018-09-20 MedSci MedSci原创

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新的研究发现肺遗传间充质干细胞（LR-MSCs）通过成纤维细胞转分化在特发性肺纤维化（IPF）的发病机制中发挥关键作用。几乎所有的纤维化肺病均存在Wnt /β-连环蛋白信号通路的异常激活，通路异常还与间充质干细胞（MSC）的分化有关。 在体外，通过测量参与Wnt /β-连环蛋白信号传导的几种关键组分的蛋白质水平，我们证实该信号传导通路在LR-MSC的肌成纤维细胞分化中被激活。通过小分子ICG

新的研究发现肺遗传间充质干细胞（LR-MSCs）通过成纤维细胞转分化在特发性肺纤维化（IPF）的发病机制中发挥关键作用。几乎所有的纤维化肺病均存在Wnt /β-连环蛋白信号通路的异常激活，通路异常还与间充质干细胞（MSC）的分化有关。

在体外，通过测量参与Wnt /β-连环蛋白信号传导的几种关键组分的蛋白质水平，我们证实该信号传导通路在LR-MSC的肌成纤维细胞分化中被激活。通过小分子ICG-001靶向抑制Wnt /β-连环蛋白信号传导，阻碍了LR-MSC的增殖和转化生长因子-β1（TGF-β1）介导的纤维化作用，呈剂量依赖性。

在体内，博来霉素处理后ICG-001通过阻断间充质-肌成纤维细胞转化，抑制基质基因表达，减少细胞凋亡来发挥其肺保护作用。此外，ICG-001的延迟给药减弱了博来霉素诱导的肺纤维化，这可能是IPF干预的一种有希望的治疗策略。有趣的是，ICG-001的抗纤维化作用是通过破坏Smad的活化来发挥作用。

总之，我们的研究表明，Wnt/β-连环蛋白信号传导可能是调节LR-MSCs肌成纤维细胞分化及其进一步参与肺纤维化发展的重要机制。

原始出处：

Honghui Cao, Cong Wang, et al., Inhibition of Wnt/β-catenin signaling suppresses myofibroblast differentiation of lung resident mesenchymal stem cells and pulmonary fibrosis. Sci Rep. 2018; 8: 13644.

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    2019-08-23 okhuali

    #肌纤维#

    0

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    2019-01-19 h.y200607_23674418

    #间充质干细#

    0

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    2019-01-14 12498e0fm90暂无昵称

    #纤维母细胞#

    0

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    2018-09-22 karmond

    #细胞分化#

    0

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    2018-09-22 zhwj

    #WNT#

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=2078032, encodeId=356f20e80322f, content=<a href='/topic/show?id=8a8580960a5' target=_blank style='color:#2F92EE;'>#肌纤维#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80960, encryptionId=8a8580960a5, topicName=肌纤维)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ea6321, createdName=okhuali, createdTime=Fri Aug 23 05:48:00 CST 2019, time=2019-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1815373, encodeId=c26018153e3a4, content=<a href='/topic/show?id=ae359e231d4' target=_blank style='color:#2F92EE;'>#间充质干细#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=97231, encryptionId=ae359e231d4, topicName=间充质干细)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b632500090, createdName=h.y200607_23674418, createdTime=Sat Jan 19 20:48:00 CST 2019, time=2019-01-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1766616, encodeId=b6a11e6661610, content=<a href='/topic/show?id=d2c6e724888' target=_blank style='color:#2F92EE;'>#纤维母细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77248, encryptionId=d2c6e724888, topicName=纤维母细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=342437842399, createdName=12498e0fm90暂无昵称, createdTime=Mon Jan 14 14:48:00 CST 2019, time=2019-01-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1570231, encodeId=152615e0231ff, content=<a href='/topic/show?id=a66ae7809b1' target=_blank style='color:#2F92EE;'>#细胞分化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77809, encryptionId=a66ae7809b1, topicName=细胞分化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=653c15636865, createdName=karmond, createdTime=Sat Sep 22 11:48:00 CST 2018, time=2018-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1598612, encodeId=f813159861223, content=<a href='/topic/show?id=c4da18e2588' target=_blank style='color:#2F92EE;'>#WNT#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18725, encryptionId=c4da18e2588, topicName=WNT)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=eb3518632538, createdName=zhwj, createdTime=Sat Sep 22 11:48:00 CST 2018, time=2018-09-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=345880, encodeId=ecd7345880c7, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=82311653708, createdName=医者仁心5538, createdTime=Thu Sep 20 21:26:20 CST 2018, time=2018-09-20, status=1, ipAttribution=)]
    2018-09-20 医者仁心5538

    学习了

    0