MicroRNA 29 targets nuclear factor-κB-repressing factor and Claudin 1 to increase intestinal permeability.
MicroRNA 29 targets nuclear factor-κB-repressing factor and Claudin 1 to increase intestinal permeability.
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DOI：
10.1053/j.gastro.2014.09.037
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发表时间：
2015-01
期刊：
影响因子：
29.4
通讯作者：
Verne GN
中科院分区：
文献类型：
--
作者：
Zhou Q;Costinean S;Croce CM;Brasier AR;Merwat S;Larson SA;Basra S;Verne GN
一些患有腹泻型肠易激综合征（IBS-D）的患者具有肠道通透性过高，这有助于他们的腹泻和腹痛。MicroRNA 29（MIR 29）调节IBS-D患者的肠道通透性。我们研究并寻找MIR 29的靶点，并研究了破坏小鼠中的MIR 29的影响。我们研究了在内窥镜检查期间从患有IBS的患者（n = 183）和没有IBS的患者（对照组）（n = 36）收集的肠活检组织中的MIR 29 A和B的表达。水平与疾病表型相关。我们还产生并研究了Mir 29 −/−小鼠，其中Mir 29 a和B的表达丢失，但c没有。通过给予2，4，6-三硝基苯磺酸诱导结肠炎;收集肠组织并评估渗透性。使用来自Mir 29 −/−小鼠的组织进行微阵列分析。在用抗MIRs敲低MIR 29后，在人结肠上皮细胞和小肠上皮细胞中测量靶基因水平的变化。来自IBS-D患者的肠组织（但不是IBS伴便秘或对照组）的MIR 29 A和B水平升高，但Claudin-1（CLDN 1）和核因子-κ B-抑制因子（NKRF）水平降低。结肠炎和避水应激的诱导增加了野生型小鼠中Mir 29 a和Mir 29 b的水平以及肠道通透性;这些增加了结肠中Mir 29 −/−小鼠的肠道通透性。在微阵列和敲除实验中，发现MIR 29 A和B降低NKRF和CLDN 1信使RNA的水平，并改变调节肠通透性的其他信使RNA的水平。基于基因敲除小鼠的实验和对IBS-D患者肠组织样本的分析，MIR 29靶向并降低CLDN 1和NKRF的表达，以增加肠通透性。可能会开发阻断MIR 29的策略来恢复IBS-D患者的肠道通透性。
Some patients with irritable bowel syndrome with diarrhea (IBS-D) have intestinal hyperpermeability, which contributes to their diarrhea and abdominal pain. MicroRNA 29 (MIR29) regulates intestinal permeability in patients with IBS-D. We investigated and searched for targets of MIR29 and investigated the effects of disrupting Mir29 in mice. We investigated expression MIR29A and B in intestinal biopsies collected during endoscopy from patients with IBS (n = 183) and without IBS (controls) (n = 36). Levels were correlated with disease phenotype. We also generated and studied Mir29−/− mice, in which expression of Mir29a and b, but not c, is lost. Colitis was induced by administration of 2,4,6-trinitrobenzenesulfonic acid; intestinal tissues were collected and permeability was assessed. Microarray analysis was performed using tissues from Mir29−/− mice. Changes in levels of target genes were measured in human colonic epithelial cells and small intestinal epithelial cells after knockdown of MIR29 with anti-MIRs. Intestinal tissues from patients with IBS-D (but not IBS with constipation or controls) had increased levels of MIR29A and B, but reduced levels of Claudin-1 (CLDN1) and nuclear factor-κB–repressing factor (NKRF). Induction of colitis and water avoidance stress increased levels of Mir29a and Mir29b and intestinal permeability in wild-type mice; these increased intestinal permeability in colons of far fewer Mir29−/− mice. In microarray and knockdown experiments, MIR29A and B were found to reduce levels of NKRF and CLDN1 messenger RNA, and alter levels of other messenger RNAs that regulate intestinal permeability. Based on experiments in knockout mice and analyses of intestinal tissue samples from patients with IBS-D, MIR29 targets and reduces expression of CLDN1 and NKRF to increase intestinal permeability. Strategies to block MIR29 might be developed to restore intestinal permeability in patients with IBS-D.
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影响因子：
4.8
作者：
Majewski, Pawel M.;Thurston, Robert D.;Ghishan, Fayez K.
通讯作者：
Ghishan, Fayez K.
DOI：
10.1016/j.mrgentox.2010.05.007
发表时间：
2011-06-17
影响因子：
1.9
作者：
Koturbash, Igor;Zemp, Franz;Kovalchuk, Olga
通讯作者：
Kovalchuk, Olga
影响因子：
158.5
作者：
Mayer, Emeran A.
通讯作者：
Mayer, Emeran A.
影响因子：
3.7
作者：
Creighton CJ;Hernandez-Herrera A;Jacobsen A;Levine DA;Mankoo P;Schultz N;Du Y;Zhang Y;Larsson E;Sheridan R;Xiao W;Spellman PT;Getz G;Wheeler DA;Perou CM;Gibbs RA;Sander C;Hayes DN;Gunaratne PH;Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
影响因子：
3.5
作者：
Camilleri M;Madsen K;Spiller R;Greenwood-Van Meerveld B;Verne GN
通讯作者：
Verne GN