Cell Death Dis:PRIMA-1MET可改善AEC综合征患者的皮肤糜烂

2020-04-02 MedSci原创 MedSci原创

p63是一种调节皮肤发育和体内平衡的重要的转录因子,调控许多与细胞增殖、粘附及早期分化相关基因的表达。 几种罕见的综合征患者均携带p63突变,这些综合征被称为p63相关性外胚层发育不良综合征(ED)。

p63是一种调节皮肤发育和体内平衡的重要的转录因子,调控许多与细胞增殖、粘附及早期分化相关基因的表达。 几种罕见的综合征患者均携带p63突变,这些综合征被称为p63相关性外胚层发育不良综合征(ED)。

该综合征的主要形式包括分别由DBD及SAM结构域上的p63错义突变导致的EEC和AEC综合征。 ED患者表现出多种发育缺陷,包括缺指畸形、唇腭裂和外胚层发育不良,而AEC患者常出现严重的皮肤糜烂且不能100%治愈。既往研究发现,ED衍生的iPSC表现出了表皮类型的改变。 p63属于拥有相似结构域的p53基因家族。

研究人员发现p53再激活化合物PRIMA-1MET(也称为APR-246)可挽救ED-iPSC的表皮改变,目前该化合物已用于抗癌临床实验。研究人员从两名遭受持续性皮肤糜烂的AEC患儿身上取得表皮组织培养。这两个患儿p63的SAM域上携带错义突变(I576T和I537T)。研究人员发现从AEC患者分离出的原代角质形成细胞(KCs)发生表皮分化的改变,而这一变化可通过PRIMA-1MET治疗得以恢复。

根据这些现象,研究人员将化合物配制到乳膏中,并将乳膏应用于第一例患者的右手和第二例患者的头皮。通过每日治疗,这些患者被侵蚀的皮肤重新上皮化;几周后,疼痛急剧减轻,患者的生活质量也得以改善。

p63突变体主要通过与野生型p63和p73形成聚集体来发挥显性负作用。 PRIMA-1MET在增强细胞分化的同时不会降低蛋白质的聚集,提示PRIMA-1MET可以直接靶向细胞分化,而不影响p63活性。

总而言之,该研究提示,抗肿瘤化合物PRIMA-1MET或可成为AEC皮肤糜烂的一种全身疗法。

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createdName=nakerunner, createdTime=Sat May 02 17:16:32 CST 2020, time=2020-05-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2013260, encodeId=83022013260af, content=<a href='/topic/show?id=7d69598468' target=_blank style='color:#2F92EE;'>#Dis#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5984, encryptionId=7d69598468, topicName=Dis)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c689267, createdName=cmj8wellington, createdTime=Tue Nov 10 03:16:32 CST 2020, time=2020-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1896625, encodeId=c6dc1896625eb, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Sun Sep 13 19:16:32 CST 2020, time=2020-09-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2009252, encodeId=39db2009252bb, content=<a href='/topic/show?id=bf2ae2089b6' target=_blank style='color:#2F92EE;'>#皮肤糜烂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=72089, encryptionId=bf2ae2089b6, topicName=皮肤糜烂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d8f4110, createdName=guojianrong, createdTime=Sat Oct 31 11:16:32 CST 2020, time=2020-10-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1871649, encodeId=afb218e164988, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sat Feb 20 09:16:32 CST 2021, time=2021-02-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1791475, encodeId=42b01e9147507, content=<a href='/topic/show?id=d883146e4b0' target=_blank style='color:#2F92EE;'>#PRIMA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14674, encryptionId=d883146e4b0, topicName=PRIMA)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=25c8396, createdName=ssnine, createdTime=Mon Jun 08 01:16:32 CST 2020, time=2020-06-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1431804, encodeId=e62f1431804c0, content=<a href='/topic/show?id=f9b9e9124a8' target=_blank style='color:#2F92EE;'>#综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=79124, encryptionId=f9b9e9124a8, topicName=综合征)], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/aLGWoFXAyMbIu3qymFOyheQLjPSX3OUs5GmkyBlcCOwTPIeq3why9NGibxxUqYo6hcx8qZLHZFgNPnBK1yzWeOFpyg2OnWOt0/0, createdBy=fa4716, createdName=zhouqu_8, createdTime=Sat Apr 04 12:16:32 CST 2020, time=2020-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1531568, encodeId=67961531568d4, content=<a href='/topic/show?id=770e5e9457' target=_blank style='color:#2F92EE;'>#Death#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5794, encryptionId=770e5e9457, topicName=Death)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Sat Apr 04 12:16:32 CST 2020, time=2020-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1568939, encodeId=a68d1568939e2, content=<a href='/topic/show?id=39ade6877bc' target=_blank style='color:#2F92EE;'>#糜烂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76877, encryptionId=39ade6877bc, topicName=糜烂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f13815479658, createdName=许安, createdTime=Sat Apr 04 12:16:32 CST 2020, time=2020-04-04, status=1, ipAttribution=)]
    2020-09-13 一闲
  5. [GetPortalCommentsPageByObjectIdResponse(id=1961943, encodeId=84ab19619432d, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Thu Mar 18 19:16:32 CST 2021, time=2021-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1779378, encodeId=32371e79378a7, content=<a href='/topic/show?id=c18420469f' target=_blank style='color:#2F92EE;'>#AEC综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2046, encryptionId=c18420469f, topicName=AEC综合征)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0cd7162, 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createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Sat Apr 04 12:16:32 CST 2020, time=2020-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1568939, encodeId=a68d1568939e2, content=<a href='/topic/show?id=39ade6877bc' target=_blank style='color:#2F92EE;'>#糜烂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76877, encryptionId=39ade6877bc, topicName=糜烂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f13815479658, createdName=许安, createdTime=Sat Apr 04 12:16:32 CST 2020, time=2020-04-04, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1961943, encodeId=84ab19619432d, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=docwu2019, createdTime=Thu Mar 18 19:16:32 CST 2021, time=2021-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1779378, encodeId=32371e79378a7, content=<a href='/topic/show?id=c18420469f' target=_blank style='color:#2F92EE;'>#AEC综合征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2046, encryptionId=c18420469f, topicName=AEC综合征)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0cd7162, 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  7. 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createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Sat Apr 04 12:16:32 CST 2020, time=2020-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1568939, encodeId=a68d1568939e2, content=<a href='/topic/show?id=39ade6877bc' target=_blank style='color:#2F92EE;'>#糜烂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76877, encryptionId=39ade6877bc, topicName=糜烂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f13815479658, createdName=许安, createdTime=Sat Apr 04 12:16:32 CST 2020, time=2020-04-04, status=1, ipAttribution=)]
    2020-06-08 ssnine
  8. 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  9. 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createdAvatar=null, createdBy=32e312278742, createdName=cy0328, createdTime=Sat Apr 04 12:16:32 CST 2020, time=2020-04-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1568939, encodeId=a68d1568939e2, content=<a href='/topic/show?id=39ade6877bc' target=_blank style='color:#2F92EE;'>#糜烂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=76877, encryptionId=39ade6877bc, topicName=糜烂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f13815479658, createdName=许安, createdTime=Sat Apr 04 12:16:32 CST 2020, time=2020-04-04, status=1, ipAttribution=)]
    2020-04-04 cy0328
  10. 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    2020-04-04 许安

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