MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells.
MicroRNAs miR-23a-3p, miR-23b-3p, and miR-149-5p Regulate the Expression of Proapoptotic BH3-Only Proteins DP5 and PUMA in Human Pancreatic β-Cells.
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微小RNA miR - 23a - 3p、miR - 23b - 3p和miR - 149 - 5p调控人胰岛β细胞中促凋亡BH3结构域-only蛋白DP5和PUMA的表达 。
DOI：
10.2337/db16-0592
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发表时间：
2017-01
期刊：
影响因子：
7.7
通讯作者：
Eizirik DL
中科院分区：
文献类型：
--
作者：
Grieco FA;Sebastiani G;Juan-Mateu J;Villate O;Marroqui L;Ladrière L;Tugay K;Regazzi R;Bugliani M;Marchetti P;Dotta F;Eizirik DL
1型糖尿病（T1 D）是一种导致β细胞破坏的自身免疫性疾病。microRNAs（miRNAs）是一类控制基因表达和器官形成的小分子非编码RNA。它们参与了几种自身免疫性疾病的发病机制，但导致T1 D中β细胞死亡的miRNA的性质及其靶基因仍有待澄清。我们对暴露于细胞因子IL-1β和IFN-γ的人胰岛制备物进行了miRNA表达谱。通过实时定量PCR确认人β细胞中的miRNA和靶基因修饰。使用单链miRNA抑制剂来阻断所选择的内源性miRNA。通过Hoechst/碘化丙啶染色和半胱天冬酶-3的活化来测量细胞死亡。检测到57种miRNA受细胞因子调节。其中三个，即miR-23 a-3 p，miR-23 b-3 p和miR-149- 5 p，被细胞因子下调，并被选择用于进一步研究。发现这些miRNA调节促凋亡Bcl-2蛋白DP 5和CD 4A的表达以及随后的人β细胞凋亡。这些结果鉴定了人胰腺β细胞中一个关键的miRNA家族与促凋亡Bcl-2蛋白之间的新型串扰，拓宽了我们对早期T1 D中苦参碱诱导的β细胞凋亡的理解。
Type 1 diabetes (T1D) is an autoimmune disease leading to β-cell destruction. MicroRNAs (miRNAs) are small noncoding RNAs that control gene expression and organ formation. They participate in the pathogenesis of several autoimmune diseases, but the nature of miRNAs contributing to β-cell death in T1D and their target genes remain to be clarified. We performed an miRNA expression profile on human islet preparations exposed to the cytokines IL-1β plus IFN-γ. Confirmation of miRNA and target gene modification in human β-cells was performed by real-time quantitative PCR. Single-stranded miRNAs inhibitors were used to block selected endogenous miRNAs. Cell death was measured by Hoechst/propidium iodide staining and activation of caspase-3. Fifty-seven miRNAs were detected as modulated by cytokines. Three of them, namely miR-23a-3p, miR-23b-3p, and miR-149-5p, were downregulated by cytokines and selected for further studies. These miRNAs were found to regulate the expression of the proapoptotic Bcl-2 proteins DP5 and PUMA and consequent human β-cell apoptosis. These results identify a novel cross talk between a key family of miRNAs and proapoptotic Bcl-2 proteins in human pancreatic β-cells, broadening our understanding of cytokine-induced β-cell apoptosis in early T1D.
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影响因子：
4.8
作者：
Gurzov, Esteban N.;Germano, Carla M.;Eizirik, Decio L.
通讯作者：
Eizirik, Decio L.
影响因子：
15.9
作者：
Hoorens, A;VandeCasteele, M;Pipeleers, D
通讯作者：
Pipeleers, D
miR-146a 和 miR-155 基因的超级增强子有助于炎症的自我调节
DOI：
10.1016/j.bbagrm.2016.02.004
发表时间：
2016-04-01
影响因子：
4.7
作者：
Duan, Qiong;Mao, Xiaoxiao;Yang, Tianlun
通讯作者：
Yang, Tianlun
影响因子：
7.7
作者：
Cardozo, AK;Kruhoffer, M;Eizirik, DL
通讯作者：
Eizirik, DL
影响因子：
3.5
作者：
Esguerra JL;Mollet IG;Salunkhe VA;Wendt A;Eliasson L
通讯作者：
Eliasson L