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Circulation.：MicroRNA93-IRF9-IRG1-衣康酸途径调节M2样巨噬细胞极化重建缺血性肌肉血运

2017-04-05 MedSci MedSci原创

MicroRNA93IRF9IRG1衣康酸巨噬细胞
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目前尚无治疗和改善严重外周动脉疾病（PAD）患者的方法。之前研究报道miR93调节血管生成并减少遗传性PAD模型的组织损失。然而，miR93介导的缺血性肌肉的新生血管形成中细胞特异性功能、下游机制或信号传导尚不清楚。巨噬细胞调节PAD中的血管生成，并且这一程度取决于M2对M1的激活/极化状态。本研究中，我们发现miR93通过调节巨噬细胞极化在PAD模型中促进血管和动脉生成改善缺血肌肉血运重建的新机

目前尚无治疗和改善严重外周动脉疾病（PAD）患者的方法。之前研究报道miR93调节血管生成并减少遗传性PAD模型的组织损失。然而，miR93介导的缺血性肌肉的新生血管形成中细胞特异性功能、下游机制或信号传导尚不清楚。巨噬细胞调节PAD中的血管生成，并且这一程度取决于M2对M1的激活/极化状态。本研究中，我们发现miR93通过调节巨噬细胞极化在PAD模型中促进血管和动脉生成改善缺血肌肉血运重建的新机制。

在PAD术后 与野生型（WT）相比，miR106b-93-25簇缺陷小鼠（miR106b-93-25 - / - ）的血管和动脉生成减少，伴随M1样巨噬细胞增加。给予miR106b-93-25 - / - PAD小鼠肌肉注射miR93增加了血管生成、动脉发生、灌注程度，这都与近端远端后肢肌肉中M2样巨噬细胞增多相关。在体外，即使是M1样极化刺激下，miR93也促进并维持M2样巨噬细胞极化。将miR106b-93-25 - / - 小鼠的骨髓巨噬细胞输送给WT小鼠缺血肌肉可减少其血管生成、动脉发生和灌注程度，而野生型巨噬细胞转移到miR106b-93-25 - / - 具有相反效应。 将miR106b-93-25 - / - 与WT缺血肌肉做RNA序列分析，miR93调节IRG1功能、衣康酸的产生和巨噬细胞极化。3'UTR荧光素酶测定发现IRG1不是miR93的直接靶标，但是调节IRG1表达的IRF9是miR93靶标。体外实验证实，IRF9、IRG1和衣康酸治疗显着抑制内皮血管生成。

我们发现miR93抑制IRF9降低IRG1-衣康酸产生，诱导缺血性肌肉中的M2样巨噬细胞极化，增强PAD模型中的血管生成、动脉产生和灌注恢复。

原始出处：Ganta VC， Choi MH，et al.A MicroRNA93-IRF9-IRG1-Itaconic Acid Pathway Modulates M2-like-Macrophage Polarization to Revascularize Ischemic Muscle. Circulation. 2017 Mar 29. pii： CIRCULATIONAHA.116.025490.

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    2017-09-21 xjy02

    #Micro#

    0

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    2017-06-03 yb6560

    #衣康酸#

    0

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    2017-09-05 jiafufeng@yaho

    #CRO#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=2084186, encodeId=4c0120841861a, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Thu Sep 21 03:00:00 CST 2017, time=2017-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2009958, encodeId=425e200995843, content=<a href='/topic/show?id=5d539010884' target=_blank style='color:#2F92EE;'>#衣康酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=90108, encryptionId=5d539010884, topicName=衣康酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, createdName=yb6560, createdTime=Sat Jun 03 22:00:00 CST 2017, time=2017-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857417, encodeId=a07f185e417af, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Tue Sep 05 20:00:00 CST 2017, time=2017-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2079872, encodeId=a15c20e9872e3, content=<a href='/topic/show?id=0d4511e4505' target=_blank style='color:#2F92EE;'>#MicroRNA93#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11745, encryptionId=0d4511e4505, topicName=MicroRNA93)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=52c7237, createdName=yahu, createdTime=Thu Jan 25 08:00:00 CST 2018, time=2018-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1892845, encodeId=c33b189284505, content=<a href='/topic/show?id=c738e93521f' target=_blank style='color:#2F92EE;'>#缺血性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79352, encryptionId=c738e93521f, topicName=缺血性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=66ec123, createdName=guihongzh, createdTime=Fri Jan 05 08:00:00 CST 2018, time=2018-01-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=185600, encodeId=c024185600df, content=优质资源，共同分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, 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 19:00:14 CST 2017, time=2017-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1435687, encodeId=0d95143568e90, content=<a href='/topic/show?id=31df11e1642' target=_blank style='color:#2F92EE;'>#microRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11716, encryptionId=31df11e1642, topicName=microRNA)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Thu Apr 06 15:00:00 CST 2017, time=2017-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1597871, encodeId=5f18159e871d6, content=<a href='/topic/show?id=b1e3e7926ba' target=_blank style='color:#2F92EE;'>#细胞极化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77926, encryptionId=b1e3e7926ba, topicName=细胞极化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d3e318558301, createdName=tastas, createdTime=Thu Apr 06 15:00:00 CST 2017, time=2017-04-06, status=1, ipAttribution=)]
    2018-01-25 yahu

    #MicroRNA93#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=2084186, encodeId=4c0120841861a, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, createdName=xjy02, createdTime=Thu Sep 21 03:00:00 CST 2017, time=2017-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2009958, encodeId=425e200995843, content=<a href='/topic/show?id=5d539010884' target=_blank style='color:#2F92EE;'>#衣康酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=90108, encryptionId=5d539010884, topicName=衣康酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4b65161, createdName=yb6560, createdTime=Sat Jun 03 22:00:00 CST 2017, time=2017-06-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857417, encodeId=a07f185e417af, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Tue Sep 05 20:00:00 CST 2017, time=2017-09-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2079872, encodeId=a15c20e9872e3, content=<a href='/topic/show?id=0d4511e4505' target=_blank style='color:#2F92EE;'>#MicroRNA93#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11745, encryptionId=0d4511e4505, topicName=MicroRNA93)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=52c7237, createdName=yahu, createdTime=Thu Jan 25 08:00:00 CST 2018, time=2018-01-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1892845, encodeId=c33b189284505, content=<a href='/topic/show?id=c738e93521f' target=_blank style='color:#2F92EE;'>#缺血性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79352, encryptionId=c738e93521f, topicName=缺血性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=66ec123, createdName=guihongzh, createdTime=Fri Jan 05 08:00:00 CST 2018, time=2018-01-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=185600, encodeId=c024185600df, content=优质资源，共同分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=81, 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 19:00:14 CST 2017, time=2017-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1435687, encodeId=0d95143568e90, content=<a href='/topic/show?id=31df11e1642' target=_blank style='color:#2F92EE;'>#microRNA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11716, encryptionId=31df11e1642, topicName=microRNA)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Thu Apr 06 15:00:00 CST 2017, time=2017-04-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1597871, encodeId=5f18159e871d6, content=<a href='/topic/show?id=b1e3e7926ba' target=_blank style='color:#2F92EE;'>#细胞极化#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77926, encryptionId=b1e3e7926ba, topicName=细胞极化)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d3e318558301, createdName=tastas, createdTime=Thu Apr 06 15:00:00 CST 2017, time=2017-04-06, status=1, ipAttribution=)]
    2018-01-05 guihongzh

    #缺血性#

    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 zhouqu_8

    #microRNA#

    0

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    2017-04-06 tastas

    #细胞极化#

    0

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