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Toxicol Lett：霉菌毒素赭曲霉毒素A和桔霉素在纳摩尔浓度下协同促进肾疾病的进展

2018-06-04 MedSci MedSci原创

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食物中赭曲霉毒素A（OTA）或桔霉素（CIT）浓度增加与肾小管间质性肾病的患病率增加相关。我们测试了这样的假设：人类近端小管衍生的上皮细胞（HK-2）与OTA和CIT共培养促进炎症因子/上皮细胞间质转化（EMT）或纤维化的发生。我们测量了炎症标志物，EMT和纤维化，并研究了MAP激酶的作用。在纳摩尔浓度下同时而非单独暴露于OTA和CIT导致（i）TNF蛋白和mRNA的表达增加，（ii）COX-2蛋

食物中赭曲霉毒素A（OTA）或桔霉素（CIT）浓度增加与肾小管间质性肾病的患病率增加相关。我们测试了这样的假设：人类近端小管衍生的上皮细胞（HK-2）与OTA和CIT共培养促进炎症因子/上皮细胞间质转化（EMT）或纤维化的发生。

我们测量了炎症标志物，EMT和纤维化，并研究了MAP激酶的作用。在纳摩尔浓度下同时而非单独暴露于OTA和CIT导致（i）TNF蛋白和mRNA的表达增加，（ii）COX-2蛋白和mRNA的表达减少，（iii）E-钙粘蛋白蛋白和（iv）波形蛋白和α-SMA蛋白的表达增加。

细胞形状从鹅卵石转变为纺锤样表型，表明EMT。胞外和胞内胶原III蛋白的含量增加。TNF、COX-2、E-钙粘蛋白和α-SMA的表达随mRNA的表达而改变，表明转录调控。但是vimentin和胶原蛋白III mRNA并非如此，说明转录后调节。ERK 1/2和JNK 1/2的抑制减少了对TNF的作用，但对α-SMA mRNA没有影响，表明这些激酶参与了此过程。暴露于CIT或OTA，或联合霉菌毒素后ERK1/2的磷酸化增加。相比之下，JNK1/2的磷酸化并没有变化。

总之，该研究结果表明，纳摩尔OTA和CIT协同作用可促进肾脏疾病进程。

原始出处：

Schulz MC1, Schumann L, et al., Synergistic action of the nephrotoxic mycotoxins ochratoxin A and citrinin at nanomolar concentrations in human proximal tubule-derived cells. Toxicol Lett. 2018 Jul;291:149-157. doi: 10.1016/j.toxlet.2018.04.014. Epub 2018 Apr 17.

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  1. [GetPortalCommentsPageByObjectIdResponse(id=1723837, encodeId=0f761e2383773, content=<a href='/topic/show?id=36ea988949a' target=_blank style='color:#2F92EE;'>#霉菌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98894, encryptionId=36ea988949a, topicName=霉菌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6bd333549766, createdName=qingrejiedu, createdTime=Fri Sep 21 03:47:00 CST 2018, time=2018-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1544528, encodeId=59f6154452876, content=<a href='/topic/show?id=ac3d6549e75' target=_blank style='color:#2F92EE;'>#浓度#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65497, encryptionId=ac3d6549e75, topicName=浓度)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=16b213663040, createdName=12498974m55暂无昵称, createdTime=Wed Jun 06 03:47:00 CST 2018, time=2018-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=321452, encodeId=005b321452b9, content=学习了.涨知识了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDM9swhbgTo7nzqRKzMmzckmEoeTyLQVDCgjqsicjyhxPs0vPoYU6GsSYbCjSkNHicJkz3NL0a0EbUMVdNjkctXI6FocpGKaVr9E/0, createdBy=29392048316, createdName=王秀, createdTime=Mon Jun 04 14:06:44 CST 2018, time=2018-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=321451, encodeId=61a7321451de, content=曲霉毒素和橘霉素协同作用对人体危害更大., beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzcjoLTEEgkSSQ8pVIiaf4a4INaoMLBV16QEk3dvvBRpicwIwmDGv0jePErJ4aE9ibVBDPtkialQLT9Bs/0, createdBy=04811949400, createdName=邓启付, createdTime=Mon Jun 04 14:00:42 CST 2018, time=2018-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=321449, encodeId=2e3632144927, content=挺好, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acef1880472, createdName=gukekzd, createdTime=Mon Jun 04 13:30:31 CST 2018, time=2018-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=321448, encodeId=5dda321448f4, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acef1880472, createdName=gukekzd, createdTime=Mon Jun 04 13:28:47 CST 2018, time=2018-06-04, status=1, ipAttribution=)]
    2018-09-21 qingrejiedu

    #霉菌#

    0

  2. [GetPortalCommentsPageByObjectIdResponse(id=1723837, encodeId=0f761e2383773, content=<a href='/topic/show?id=36ea988949a' target=_blank style='color:#2F92EE;'>#霉菌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98894, encryptionId=36ea988949a, topicName=霉菌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6bd333549766, createdName=qingrejiedu, createdTime=Fri Sep 21 03:47:00 CST 2018, time=2018-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1544528, encodeId=59f6154452876, content=<a href='/topic/show?id=ac3d6549e75' target=_blank style='color:#2F92EE;'>#浓度#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65497, encryptionId=ac3d6549e75, topicName=浓度)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=16b213663040, createdName=12498974m55暂无昵称, createdTime=Wed Jun 06 03:47:00 CST 2018, time=2018-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=321452, encodeId=005b321452b9, content=学习了.涨知识了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDM9swhbgTo7nzqRKzMmzckmEoeTyLQVDCgjqsicjyhxPs0vPoYU6GsSYbCjSkNHicJkz3NL0a0EbUMVdNjkctXI6FocpGKaVr9E/0, createdBy=29392048316, createdName=王秀, createdTime=Mon Jun 04 14:06:44 CST 2018, time=2018-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=321451, encodeId=61a7321451de, content=曲霉毒素和橘霉素协同作用对人体危害更大., beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzcjoLTEEgkSSQ8pVIiaf4a4INaoMLBV16QEk3dvvBRpicwIwmDGv0jePErJ4aE9ibVBDPtkialQLT9Bs/0, createdBy=04811949400, createdName=邓启付, createdTime=Mon Jun 04 14:00:42 CST 2018, time=2018-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=321449, encodeId=2e3632144927, content=挺好, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acef1880472, createdName=gukekzd, createdTime=Mon Jun 04 13:30:31 CST 2018, time=2018-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=321448, encodeId=5dda321448f4, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acef1880472, createdName=gukekzd, createdTime=Mon Jun 04 13:28:47 CST 2018, time=2018-06-04, status=1, ipAttribution=)]
    2018-06-06 12498974m55暂无昵称

    #浓度#

    0

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    2018-06-04 王秀

    学习了.涨知识了!

    0

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    2018-06-04 邓启付

    曲霉毒素和橘霉素协同作用对人体危害更大.

    0

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    2018-06-04 gukekzd

    挺好

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1723837, encodeId=0f761e2383773, content=<a href='/topic/show?id=36ea988949a' target=_blank style='color:#2F92EE;'>#霉菌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=98894, encryptionId=36ea988949a, topicName=霉菌)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6bd333549766, createdName=qingrejiedu, createdTime=Fri Sep 21 03:47:00 CST 2018, time=2018-09-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1544528, encodeId=59f6154452876, content=<a href='/topic/show?id=ac3d6549e75' target=_blank style='color:#2F92EE;'>#浓度#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=65497, encryptionId=ac3d6549e75, topicName=浓度)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=16b213663040, createdName=12498974m55暂无昵称, createdTime=Wed Jun 06 03:47:00 CST 2018, time=2018-06-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=321452, encodeId=005b321452b9, content=学习了.涨知识了!, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/ajNVdqHZLLDM9swhbgTo7nzqRKzMmzckmEoeTyLQVDCgjqsicjyhxPs0vPoYU6GsSYbCjSkNHicJkz3NL0a0EbUMVdNjkctXI6FocpGKaVr9E/0, createdBy=29392048316, createdName=王秀, createdTime=Mon Jun 04 14:06:44 CST 2018, time=2018-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=321451, encodeId=61a7321451de, content=曲霉毒素和橘霉素协同作用对人体危害更大., beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/jW482SpianMayicTRbRZ5RzcjoLTEEgkSSQ8pVIiaf4a4INaoMLBV16QEk3dvvBRpicwIwmDGv0jePErJ4aE9ibVBDPtkialQLT9Bs/0, createdBy=04811949400, createdName=邓启付, createdTime=Mon Jun 04 14:00:42 CST 2018, time=2018-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=321449, encodeId=2e3632144927, content=挺好, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acef1880472, createdName=gukekzd, createdTime=Mon Jun 04 13:30:31 CST 2018, time=2018-06-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=321448, encodeId=5dda321448f4, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=acef1880472, createdName=gukekzd, createdTime=Mon Jun 04 13:28:47 CST 2018, time=2018-06-04, status=1, ipAttribution=)]
    2018-06-04 gukekzd

    学习了

    0