MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome.
MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome.
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DOI：
10.1136/gut.2009.181834
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发表时间：
2010-06
期刊：
影响因子：
24.5
通讯作者：
Verne GN
中科院分区：
文献类型：
--
作者：
Zhou Q;Souba WW;Croce CM;Verne GN
肠易激综合征（IBS）的病理生理学基础的分子机制知之甚少。一种机制可能涉及增加肠道通透性，补充谷氨酰胺可逆转这种情况。我们的目标是评估谷氨酰胺合成酶及其互补miRNA在肠膜通透性增加的IBS患者的血液微泡和肠组织中的表达。我们使用乳果糖/甘露醇法评价了19例以肠易激综合征为主的IBS患者和10例对照组的肠膜通透性。在血液微泡和肠道组织中评估miRNA表达。为了进一步证实miRNA与谷氨酰胺合成酶表达之间的关系，进行了细胞培养实验。谷氨酰胺合成酶也在患者的肠道组织中进行了评价。与膜通透性正常的IBS患者和对照组相比，IBS患者的一个子集（8/19，42%）具有增加的肠膜通透性和减少的谷氨酰胺合成酶表达。肠黏膜通透性增加的IBS患者血微泡、小肠和结肠组织中miR-29 a表达增加。增加的肠通透性由miR-29 a调节，miR-29 a在GLUL基因的3 '-UTR中具有互补位点。结果支持GLUL调节肠膜通透性和miR-29 a调节GLUL和肠膜通透性的结论。这些数据表明，miR-29 a对肠膜通透性的影响可能是由于其对GLUL的调节。靶向这一信号通路可能会导致一种新的治疗方法来治疗IBS患者，特别是因为模拟或抑制基于miRNA的机制的小分子很容易获得。
The molecular mechanisms underlying the pathophysiology of irritable bowel syndrome (IBS) are poorly understood. One mechanism may involve increased intestinal permeability that is reversed with glutamine supplementation. Our goal was to evaluate the expression of glutamine synthetase and its complementary miRNA in blood microvesicles and gut tissues of IBS patients with increased intestinal membrane permeability. We evaluated 19 diarrhea-predominant IBS patients and 10 controls for intestinal membrane permeability using the lactulose/mannitol method. miRNA expression was evaluated in blood microvesicles and gut tissue. To further confirm the relationship between miRNA and glutamine synthetase expression, cell culture experiments were conducted. Glutamine synthetase was also evaluated in the gut tissues of patients. A subset of IBS patients (8/19, 42%) had increased intestinal membrane permeability and decreased glutamine synthetase expression compared to IBS patients with normal membrane permeability and to controls. Expression of miR-29a was increased in blood microvesicles, small bowel and colon tissues of IBS patients with increased intestinal membrane permeability. Increased intestinal permeability was modulated by miR-29a which has a complementary site in the 3'-UTR of the GLUL gene. The results support the conclusion that GLUL regulates intestinal membrane permeability and miR-29a regulates both GLUL and intestinal membrane permeability. The data suggests that miR-29a effects on intestinal membrane permeability may be due to its regulation of GLUL. Targeting this signaling pathway could lead to a new therapeutic approach to the treatment of patients with IBS, especially because small molecules that mimic or inhibit miRNA-based mechanisms are readily available.
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影响因子：
3.7
作者：
Halicka, HD;Bedner, E;Darzynkiewicz, Z
通讯作者：
Darzynkiewicz, Z
影响因子：
2
作者：
Horstman, Lawrence L.;Jy, Wenche;Ahn, Yeon S.
通讯作者：
Ahn, Yeon S.
影响因子：
56.9
作者：
Farh, KKH;Grimson, A;Bartel, DP
通讯作者：
Bartel, DP
DOI：
10.1073/pnas.2333854100
发表时间：
2004-01-06
影响因子：
11.1
作者：
Kim, J;Krichevsky, A;Ruvkun, G
通讯作者：
Ruvkun, G
影响因子：
4.2
作者：
DeMarco, V;Dyess, K;Neu, J
通讯作者：
Neu, J