DIABETOLOGIA:Müller细胞中X-box结合蛋白1的缺失增加了糖尿病小鼠模型中的视网膜炎症

2019-04-03 不详 网络

Müller<span style="font-size:12.0pt;font-family:宋体;mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin;mso-fareast-font-family:宋体;mso-fareast-theme-font: minor-fareast;mso-hansi-font-fam

Müller胶质细胞(MG)是视网膜细胞因子的主要来源,其活化与糖尿病视网膜病变中的视网膜炎症和血管渗漏密切相关。以前,我们证明X-box结合蛋白1XBP1)是糖尿病视网膜病变中由内质网(ER)应激激活的转录因子,参与视网膜内皮细胞炎症的调节。现在,我们探讨了XBP1ER应激在调节MG衍生的促炎因子中的作用,以及它们对糖尿病视网膜病变中血管通透性的影响。

通过将Xbp1 flox / flox小鼠与Müller-Cre转基因小鼠杂交产生MG特异性条件性Xbp1敲除(Xbp1Müller - / -)小鼠。通过用链脲佐菌素诱导模拟糖尿病,并且在诱导后2个月用FITC-缀合的葡聚糖测量视网膜血管通透性。从Xbp1Müller - / -Xbp1Müller + / +小鼠中分离初级Müller细胞,并暴露于缺氧和高水平的葡萄糖。通过实时PCR,蛋白质印迹或免疫组织化学检查ER应激和炎性因子的水平。

结果显示, XBP1 穆勒- / -小鼠表现出正常视网膜发育和视网膜功能,表达ER应激的相似水平和炎症基因XBP1 穆勒+ / + 在糖尿病诱导的条件下,相比XBP1 米勒+ / +小鼠中,XBP1 穆勒- / -小鼠视网膜Vegf(也称为VEGFA)和TNF-α(也称为肿瘤坏死因子)和ER应激的标志物基因Grp78(也称为Hspa5Atf4Chop(也称为Ddit3)的mRNA水平更高,Atf6和血管内皮生长因子(VEGF),TNF-α,磷酸化c-Jun N-末端激酶(JNK),78 kDa葡萄糖调节蛋白(GRP78),磷酸真核翻译起始因子(eIF和激活转录因子(ATF6蛋白水平更高。与糖尿病XBP1 穆勒+ / +小鼠相比,XBP1 穆勒- / -小鼠视网膜血管渗透性是更高(p  <0.01)。来自分离的原代Müller细胞体外获得的结果证实XBP1 穆勒- / -小鼠中的炎性和ER应激标记物比(但不是GRP78XBP1 穆勒+ / +老鼠细胞中表达水平更高此外,此外,与Xbp1Muller +/+小鼠相比,缺乏xbp1Muller细胞更容易受到高糖或缺氧诱导的ER应激和炎症的影响。抑制ER应激与化学陪伴抑制低氧诱导VEGFTNF-α生产XBP1-deficient Muller细胞。

我们的研究结果揭示了XBP1和内质网应激在mg驱动的视网膜炎症中的重要作用,提示靶向内质网应激可能是预防和治疗糖尿病视网膜病变的一种有前景的方法。

原始出处:

Loss of X-box binding protein 1 in Müller cells augments retinal inflammation in a mouse model of diabetes

Jing YangChen ChenTodd McLaughlin,

本文系梅斯医学(MedSci)原创编译整理,转载需授权!


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    2019-04-05 zutt
  5. [GetPortalCommentsPageByObjectIdResponse(id=1751402, encodeId=4c131e51402f1, content=<a href='/topic/show?id=138290e787c' target=_blank style='color:#2F92EE;'>#视网膜炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=90778, encryptionId=138290e787c, topicName=视网膜炎)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d03036305261, createdName=Tommy1961, createdTime=Thu Feb 20 20:52:00 CST 2020, time=2020-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1639050, encodeId=e0521639050d6, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Thu Aug 08 12:52:00 CST 2019, time=2019-08-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1761061, encodeId=16881e6106120, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Fri Jun 14 16:52:00 CST 2019, time=2019-06-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1270181, encodeId=84bb12e01819a, 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=27, 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=Fri Apr 05 10:52:00 CST 2019, time=2019-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436797, encodeId=febd1436e979b, content=<a href='/topic/show?id=a9424e199a5' target=_blank style='color:#2F92EE;'>#小鼠模型#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47199, encryptionId=a9424e199a5, topicName=小鼠模型)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Fri Apr 05 10:52:00 CST 2019, time=2019-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1042348, encodeId=c24f104234894, content=谢谢MedSci提供最新的资讯, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Wed Apr 03 22:52:00 CST 2019, time=2019-04-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1047690, encodeId=b2b0104e690cc, content=梅斯里提供了很多疾病的模型计算公式,赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Wed Apr 03 22:52:00 CST 2019, time=2019-04-03, status=1, ipAttribution=)]
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    2019-04-03 misszhang

    谢谢MedSci提供最新的资讯

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1751402, encodeId=4c131e51402f1, content=<a href='/topic/show?id=138290e787c' target=_blank style='color:#2F92EE;'>#视网膜炎#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=90778, encryptionId=138290e787c, topicName=视网膜炎)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=d03036305261, createdName=Tommy1961, createdTime=Thu Feb 20 20:52:00 CST 2020, time=2020-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1639050, encodeId=e0521639050d6, content=<a href='/topic/show?id=afda591646' target=_blank style='color:#2F92EE;'>#DIA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5916, encryptionId=afda591646, topicName=DIA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=987022654425, createdName=ms9608593228839890, createdTime=Thu Aug 08 12:52:00 CST 2019, time=2019-08-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1761061, encodeId=16881e6106120, content=<a href='/topic/show?id=9bea33520d' target=_blank style='color:#2F92EE;'>#BET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3352, encryptionId=9bea33520d, topicName=BET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9a1a37427546, createdName=ms5439512287675881, createdTime=Fri Jun 14 16:52:00 CST 2019, time=2019-06-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1270181, encodeId=84bb12e01819a, 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=27, 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=Fri Apr 05 10:52:00 CST 2019, time=2019-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1436797, encodeId=febd1436e979b, content=<a href='/topic/show?id=a9424e199a5' target=_blank style='color:#2F92EE;'>#小鼠模型#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47199, encryptionId=a9424e199a5, topicName=小鼠模型)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Fri Apr 05 10:52:00 CST 2019, time=2019-04-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1042348, encodeId=c24f104234894, content=谢谢MedSci提供最新的资讯, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Wed Apr 03 22:52:00 CST 2019, time=2019-04-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1047690, encodeId=b2b0104e690cc, content=梅斯里提供了很多疾病的模型计算公式,赞一个!, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Wed Apr 03 22:52:00 CST 2019, time=2019-04-03, status=1, ipAttribution=)]
    2019-04-03 CHANGE

    梅斯里提供了很多疾病的模型计算公式,赞一个!

    0