ZFP36 promotes VDR mRNA degradation to facilitate cell death in oral and colonic epithelial cells.
ZFP36 promotes VDR mRNA degradation to facilitate cell death in oral and colonic epithelial cells.
复制标题
ZFP36 促进 VDR mRNA 降解，促进口腔和结肠上皮细胞的细胞死亡
DOI：
10.1186/s12964-021-00765-4
复制
发表时间：
2021-08-11
期刊：
影响因子：
--
通讯作者：
Du J
中科院分区：
文献类型：
--
作者：
Wang X;Ge X;Liao W;Cao Y;Li R;Zhang F;Zhao B;Du J
维生素D受体（VDR）在口腔和结肠上皮细胞中起重要的保护作用。虽然我们知道VDR在自身免疫性疾病的粘膜上皮层中表达减少，但VDR减少的机制仍不清楚。采用实时荧光定量PCR、western blot和免疫染色检测人标本和细胞系中VDR和锌指蛋白36 （ZFP36）水平。荧光素酶报告法检测VDR基因启动子中的顺式元件，实时荧光定量PCR检测mRNA衰变，western blot检测蛋白降解情况。采用RNA亲和层析法检测蛋白- mrna相互作用。免疫共沉淀法检测蛋白-蛋白相互作用。荧光素酶报告法检测ZFP36在VDR mRNA 3 '非翻译区（UTR）富au元素（AREs）中的作用。我们发现ZFP36可以与VDR mRNA 3'UTR中的AREs结合，导致口腔和结肠上皮细胞在炎症情况下mRNA降解。无论是ZFP36蛋白还是VDR mRNA突变的AREs都可以消除这种蛋白-mRNA的结合过程。关键氨基酸突变后，ZFP36无法降低VDR mRNA的表达。我们还发现VDR与Y盒结合蛋白1 （YBX-1）物理结合，以阻断YBX-1的核易位并改善炎症存在时的细胞死亡。这些发现为炎症条件下口腔和结肠上皮细胞VDR减少的原因提供了见解，并解释了VDR如何维持这些细胞的细胞活力。视频摘要在线版本包含补充材料，可在10.1186/s12964-021-00765-4获得。
Vitamin D receptor (VDR) plays a vital protective role in oral and colonic epithelial cells. Albeit we know that VDR expression is reduced in the mucosal epithelial layers of autoimmune diseases, the mechanism by which VDR is decreased remains elusive. VDR and zinc finger protein 36 (ZFP36) levels in human samples and cell lines were detected by real-time PCR, western blot and immunostaining. Luciferase report assay was used to test cis-elements in VDR gene promoter, real-time PCR was applied to measure mRNA decay and western blot was performed to evaluate protein degradation. RNA affinity chromatography assay was used to test protein-mRNA interaction. Co-immunoprecipitation was used to detect protein–protein interaction. The role of ZFP36 in AU-rich elements (AREs) in the 3′ untranslated region (UTR) of VDR mRNA was also measured by luciferase report assay. We identify ZFP36 can bind with the AREs in the 3’UTR of VDR mRNA, leading to mRNA degradation in oral and colonic epithelial cells under inflammatory circumstance. Either ZFP36 protein or AREs of VDR mRNA mutation abolishes this protein-mRNA binding process. After the key amino acid’s mutation, ZFP36 fails to decrease VDR mRNA expression. We also find that VDR physically binds with Y box-binding protein 1 (YBX-1) to block YBX-1’s nuclear translocation and ameliorate cell death in the presence of inflammation. These findings provide insights into the cause of VDR decrease in oral and colonic epithelial cells under inflammatory condition and explain how VDR maintains cell viability in these cells. Video abstract The online version contains supplementary material available at 10.1186/s12964-021-00765-4.
登录
查看更多内容
影响因子：
3.8
作者：
Du, J.;Li, R.;Zhang, F.
通讯作者：
Zhang, F.
影响因子：
4.6
作者：
Choi YS;Kim Y;Yoon HJ;Baek KJ;Alam J;Park HK;Choi Y
通讯作者：
Choi Y
影响因子：
1.9
作者：
Choi YS;Baek K;Choi Y
通讯作者：
Choi Y
影响因子：
3.4
作者：
Kujundzic, Bojan;Zeljic, Katarina;Magic, Zvonko
通讯作者：
Magic, Zvonko
影响因子：
15.9
作者：
Liu, Weicheng;Chen, Yunzi;Li, Yan Chun
通讯作者：
Li, Yan Chun