MicroRNA-29a increased the intestinal membrane permeability of colonic epithelial cells in irritable bowel syndrome rats.
MicroRNA-29a increased the intestinal membrane permeability of colonic epithelial cells in irritable bowel syndrome rats.
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MicroRNA-29a增加肠易激综合征大鼠结肠上皮细胞的肠膜通透性
DOI：
10.18632/oncotarget.20687
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发表时间：
2017-10-17
期刊：
影响因子：
--
通讯作者：
Zheng X
中科院分区：
文献类型：
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作者：
Chao G;Wang Y;Zhang S;Yang W;Ni Z;Zheng X
背景腹泻型肠易激综合征（IBS-D）的整个发病机制尚不清楚。我们的目的是评估microRNA-29a（miR-29a）在IBS大鼠结肠上皮细胞中的表达变化，阐明miR-29a通过水通道蛋白（AQPs）增加肠膜通透性的机制。方法采用直肠胀压联合四肢约束法建立IBS-D大鼠模型。结肠上皮细胞分为四组。A：正常组。B: IBS-D对照组。C: IBS-D +miR-29a NC。D: IBS-D + miR-29a拮抗剂。检测miR-29a的表达、K+和乳酸脱氢酶（LDH）的浓度以及AQPs的表达。结果IBS-D对照组miR-29a表达量（2.090±0.022）高于对照组（1.00±0.031）（P<0.001）， IBS-D+miR-29a拮抗莫组miR-29a表达量（1.403±0.042）低于IBS-D对照组（P<0.001）。IBS-D对照组K+水平为1.305±0.289，低于对照组（2.171±0.204），差异有统计学意义（P<0.05）； IBS-D+miR-29a antagomir组K+水平为1.813±0.102，高于IBS-D对照组（P<0.05）。IBS-D对照组LDH升高（4153.440±177.365），高于对照组（1434.573±96.111）（P<0.001）； IBS-D+miR-29a安他哥米组LDH降低（2700.473±275.414），低于IBS-D对照组（P<0.01）。IBS-D对照组AQP1、AQP3、AQP8表达较对照组降低（0.132±0.010、0.110±0.005、0.108±0.007）（P<0.001），而IBS-D+miR-29a安他哥莫组AQP1、AQP3、AQP8表达较IBS-D对照组升高（0.197±0.005、0.182±0.011、0.194±0.003）（P<0.001）。IBS-D+miR-29a阴性对照（NC）组与IBS-D+miR-29a安塔戈米尔组比较，各日期均显示与IBS-D对照组相似的趋势。结论MiR-29a通过降低AQPs的表达增加IBS-D大鼠结肠上皮细胞的肠膜通透性。
Background The whole pathogenesis of diarrhea-predominant irritable bowel syndrome(IBS-D) is poorly understood. Our goal was to evaluate the expression change of microRNA-29a(miR-29a) in colonic epithelial cells in IBS rats and clarify the mechanism of miR-29a increasing the intestinal membrane permeability through aquaporins(AQPs). Methods The IBS-D rats models were induced by rectal distention pressure combining with extremities constraint. The colonic epithelial cells were divided into four groups. A: normal group. B: IBS-D control group. C: IBS-D +miR-29a NC. D: IBS-D + miR-29a antagomir. The expression of miR-29a, the concentration of the K+ and Lactate Dehydrogenase(LDH) and the expression of AQPs were detected. Results The miR-29a expression increased in IBS-D control group(2.090±0.022) compared with the control group(1.00±0.031) (P<0.001) while it decreased in IBS-D+miR-29a antagomir group(1.403±0.042) compared with IBS-D control group(P<0.001). The K+ decreased in IBS-D control group(1.305±0.289) compared with the control group(2.171±0.204)(P<0.05) while it increased in IBS-D+miR-29a antagomir group(1.813±0.102)(P<0.05) compared with IBS-D control group. The LDH increased in IBS-D control group(4153.440±177.365) compared with the control group(1434.573±96.111)(P<0.001) while it decreased in IBS-D+miR-29a antagomir group(2700.473±275.414) compared with IBS-D control group (P<0.01). The expression of AQP1, AQP3 and AQP8 decreased in IBS-D control group(0.132±0.010,0.110±0.005,0.108±0.007) compared with the control group (P<0.001) while it increased in IBS-D+miR-29a antagomir group(0.197±0.005,0.182±0.011,0.194±0.003) compared with IBS-D control group(P<0.001). The IBS-D+miR-29a negative control(NC) group, a comparison with IBS-D+miR-29a antagomir group, each date showed the similar trend to the IBS-D control group. Conclusions MiR-29a increased the intestinal membrane permeability of colonic epithelial cells by reducing the AQPs expression in IBS-D rats.