JCC: 泛素D在IBD患者发炎的肠上皮细胞受Notch信号和TNF-α的协同作用上调

2019-04-06 不详 MedSci原创

炎症性肠病[IBD]患者的肠上皮暴露于各种促炎细胞因子,最显着的是肿瘤坏死因子α[TNF-α]。有文献已经表明,Notch信号通路也在这种上皮细胞中上调,有助于肠上皮细胞[IEC]的增殖和再生。因此本项研究的目的是在体外重现这种环境并探索所涉及的基因调控机制。

背景和目的
炎症性肠病[IBD]患者的肠上皮暴露于各种促炎细胞因子,最显着的是肿瘤坏死因子α[TNF-α]。有文献已经表明,Notch信号通路也在这种上皮细胞中上调,有助于肠上皮细胞[IEC]的增殖和再生。因此本项研究的目的是在体外重现这种环境并探索所涉及的基因调控机制。

方法
研究人员采用人IEC细胞系或患者衍生的类器官用于分析Notch和TNF-α依赖性基因表达,并进行免疫组化分析泛素D [UBD]在各种源自患者的肠组织中的表达。

结果
研究人员在人类IEC细胞系中发现Notch信号传导和TNF-α诱导的NFκB信号传导受到相互调节以促进特定基因的表达。由于Notch和TNF-α的协同作用,研究人员将UBD鉴定为最高度上调的基因之一。UBD的协同表达在转录水平受到调节,而UBD蛋白由于翻译后的蛋白酶体降解而具有极短的半衰期。在来自IBD患者的未发炎的肠组织中,UBD表达仅限于位于隐窝底部的IEC。相比之下,在发炎组织的整个隐窝中可以看到表达UBD的IEC,表明局部炎症环境的实质诱导。使用源自患者的类器官的分析一致地证实了UBD的保守的Notch和TNF-α依赖性表达。值得注意的是,英夫利昔单抗[IFX]下调了UBD表达,反映了IBD患者的有利结果。

结论
UBD是一种在IEC中表达的新型炎症相蛋白,对抗TNF-α治疗具有高度快速的反应性。

原始出处:

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    2019-04-08 bnurmamat
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    2019-04-08 karmond
  5. [GetPortalCommentsPageByObjectIdResponse(id=2068318, encodeId=c6e9206831879, content=<a href='/topic/show?id=90b8129e7bd' target=_blank style='color:#2F92EE;'>#Notch信号#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12977, encryptionId=90b8129e7bd, topicName=Notch信号)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f49517, createdName=xinmeili, createdTime=Mon Oct 28 10:09:00 CST 2019, time=2019-10-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1948457, encodeId=3605194845e25, content=<a href='/topic/show?id=48a88152191' target=_blank style='color:#2F92EE;'>#肠上皮细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81521, encryptionId=48a88152191, topicName=肠上皮细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d7532500500, createdName=12499e01m47暂无昵称, createdTime=Mon Dec 23 12:09:00 CST 2019, time=2019-12-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1263517, encodeId=f424126351e1a, content=<a href='/topic/show?id=75bc930217' target=_blank style='color:#2F92EE;'>#IBD#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9302, encryptionId=75bc930217, topicName=IBD)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=fc0372, createdName=bnurmamat, createdTime=Mon Apr 08 07:09:00 CST 2019, time=2019-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1373779, encodeId=644513e3779e3, content=<a href='/topic/show?id=eb3b129e01d' target=_blank style='color:#2F92EE;'>#Notch#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12970, encryptionId=eb3b129e01d, topicName=Notch)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ece5364, createdName=karmond, createdTime=Mon Apr 08 07:09:00 CST 2019, time=2019-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1401721, encodeId=10541401e214f, content=<a href='/topic/show?id=17e21e57943' target=_blank style='color:#2F92EE;'>#TNF#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17579, encryptionId=17e21e57943, topicName=TNF)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqjVbfRD4f4vibEcZVcvato8Qib1gGtZJiayXCMFgHrkeErSiaxdYMiabKGxY2an9muxWCkUJbjFPViaC6A/132, createdBy=e4fb2361580, createdName=snowpeakxu, createdTime=Mon Apr 08 07:09:00 CST 2019, time=2019-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1487473, encodeId=21f9148e473b5, content=<a href='/topic/show?id=ba951352387' target=_blank style='color:#2F92EE;'>#OTC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13523, encryptionId=ba951352387, topicName=OTC)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b36f8313624, createdName=ymljack, createdTime=Mon Apr 08 07:09:00 CST 2019, time=2019-04-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1533890, encodeId=fdd51533890b1, content=<a href='/topic/show?id=4be9200308c' target=_blank style='color:#2F92EE;'>#上皮细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=20030, encryptionId=4be9200308c, topicName=上皮细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3a5d12492718, createdName=lizhou0208, createdTime=Mon Apr 08 07:09:00 CST 2019, time=2019-04-08, status=1, ipAttribution=)]
    2019-04-08 snowpeakxu
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    2019-04-08 ymljack
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