Bladder overactivity involves overexpression of MicroRNA 132 and nerve growth factor.
Bladder overactivity involves overexpression of MicroRNA 132 and nerve growth factor.
复制标题
DOI：
10.1016/j.lfs.2016.10.025
复制
发表时间：
2016-12-15
期刊：
影响因子：
6.1
通讯作者：
Tyagi, Pradeep
中科院分区：
文献类型：
--
作者：
Kashyap, Mahendra;Pore, Subrata;Chancellor, Michael;Yoshimura, Naoki;Tyagi, Pradeep
在这里，我们评估了非蛋白编码microRNAs（miRs），神经生长因子和炎症分子在乙酸诱导的膀胱过度活动大鼠模型中的表达。在异氟烷麻醉下，向成年雌性Sprague-Dawley大鼠滴注生理盐水或与脂质体复合的NGF反义寡核苷酸30分钟。24小时后，在乌拉坦麻醉下（1g/kg; s.c.），以0.04ml/min的速率膀胱内灌注生理盐水或含0.25%乙酸的生理盐水2 h。CMG后，收集膀胱，研究NGF、细胞因子和8种参与膀胱功能障碍的特异性miRNAs的表达。通过膀胱壁转染编码miR-132的质粒，独立评估miR-132在膀胱过度活动中的作用。膀胱过度活动中的NGF过表达分别与miR-132和miR-221的~2倍上调和下调相关。用NGF反义核酸预处理使miR-221和miR-132的表达恢复到对照水平，并且还降低细胞因子（MCP-1和sICAM-1）的表达。miR-199 a-5 p的表达无显著变化，但miR-210、miR-212、miR-155、miR-134和miR-206的表达在实验组间保持相似。在无乙酸暴露的情况下，膀胱壁转染miR-132质粒能够独立地诱导膀胱过度活动、膀胱肥大并上调NGF和其他细胞因子的表达。总之，我们的工作揭示了miR-132在膀胱过度活动，膀胱肥大，NGF信号传导和炎症介质表达中的作用。研究结果表明，miR-132的异常表达与排尿功能障碍有关。
Here, we assessed the expression of non-protein coding microRNAs (miRs), nerve growth factor and inflammatory molecules in the rat model of acetic acid induced bladder overactivity. Under isoflurane anesthesia, adult female Sprague-Dawley rats were instilled for 30 min with either saline or NGF antisense oligonucleotides complexed with liposomes. 24h later, treated rats were exposed to either intravesical infusion of saline or saline containing 0.25% acetic acid at the rate of 0.04ml/min for 2h under urethane anesthesia (1g/kg; s.c). After CMG, bladder was harvested to study expression of NGF, cytokines and 8 specific miRNAs involved in bladder dysfunctions. The role of miR-132 in bladder overactivity was independently assessed through bladder wall transfection of plasmid encoding miR-132. NGF overexpression in bladder overactivity was associated with ~2-fold upregulation and downregulation of miR-132 and miR-221, respectively. Pretreatment with NGF antisense restored the expression of miR-221 and miR-132 to control levels and also reduced the expression of cytokines (MCP-1 and sICAM-1). There was insignificant alteration in expression of miR-199a-5p, but expression of, miR-210, miR-212, miR-155, miR-134 and miR-206 remained similar across the experimental groups. Bladder wall transfection of miR-132 plasmid in absence of acetic acid exposure was able to independently induce bladder overactivity, bladder hypertrophy and upregulate the expression of NGF and other cytokines. Overall, our work sheds light on the role of miR-132 in bladder overactivity, bladder hypertrophy, NGF signaling and expression of inflammatory mediators. Findings suggest that aberrant expression of miR-132 is involved in voiding dysfunctions.
登录
查看更多内容
影响因子：
3.7
作者：
Othumpangat S;Walton C;Piedimonte G
通讯作者：
Piedimonte G
影响因子：
4.1
作者：
Remenyi, Judit;Hunter, Christopher J.;Arthur, J. Simon C.
通讯作者：
Arthur, J. Simon C.
影响因子：
1.7
作者：
Oddiah, D;Anand, P;Rattray, M
通讯作者：
Rattray, M
影响因子：
3.7
作者：
Heinrich M;Oberbach A;Schlichting N;Stolzenburg JU;Neuhaus J
通讯作者：
Neuhaus J
影响因子：
5.3
作者：
Eacker SM;Dawson TM;Dawson VL
通讯作者：
Dawson VL