Myocardin and microRNA-1 modulate bladder activity through connexin 43 expression during post-natal development.
Myocardin and microRNA-1 modulate bladder activity through connexin 43 expression during post-natal development.
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DOI：
10.1002/jcp.24333
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发表时间：
2013-09
影响因子：
5.6
通讯作者：
Miano JM
中科院分区：
文献类型：
--
作者：
Imamura M;Sugino Y;Long X;Slivano OJ;Nishikawa N;Yoshimura N;Miano JM
膀胱过度活动症（OAB）是一个普遍存在的临床问题，涉及神经源性和肌源性活动的改变。虽然在了解OAB的神经源性输入方面取得了一些进展，但控制肌源性膀胱活动的机制尚不清楚。我们报告了myocardin（MYOCD）和microRNA-1（miR-1）参与调节连接蛋白43（GJA 1），这是膀胱平滑肌中的一个主要间隙连接，以及这些分子在出生后膀胱发育过程中的集体作用。野生型（WT）小鼠膀胱显示从出生后早期到成年的正常发育，包括膀胱容量增加和维持对胆碱能药物的正常敏感性，同时伴有MYOCD和几种平滑肌细胞（SMC）收缩基因的下调。Myocardin异源性基因敲除小鼠表现出Myocd mRNA和几个SMC收缩基因的表达减少，同时膀胱SMC超敏反应是由间隙连接介导的。在培养的大鼠膀胱SMC和体内膀胱中，MYOCD通过上调miR-1下调GJA 1表达。有趣的是，与WT小鼠相比，成年心肌蛋白异质性敲除小鼠显示膀胱和体重正常增加，但膀胱容量较低。这些结果表明MYOCD通过上调miR-1下调GJA 1表达，从而有助于维持正常敏感性和膀胱容量的发育。
Overactive bladder (OAB) is a pervasive clinical problem involving alterations in both neurogenic and myogenic activity. While there has been some progress in understanding neurogenic inputs to OAB, the mechanisms controlling myogenic bladder activity are unclear. We report the involvement of myocardin (MYOCD) and microRNA-1 (miR-1) in the regulation of connexin 43 (GJA1), a major gap junction in bladder smooth muscle, and the collective role of these molecules during post-natal bladder development. Wild-type (WT) mouse bladders showed normal development from early post-natal to adult including increases in bladder capacity and maintenance of normal sensitivity to cholinergic agents concurrent with down-regulation of MYOCD and several smooth muscle cell (SMC) contractile genes. Myocardin heterozygous-knockout mice exhibited reduced expression of Myocd mRNA and several SMC contractile genes concurrent with bladder SMC hypersensitivity that was mediated by gap junctions. In both cultured rat bladder SMC and in vivo bladders, MYOCD down-regulated GJA1 expression through miR-1 up-regulation. Interestingly, adult myocardin heterozygous-knockout mice showed normal increases in bladder and body weight but lower bladder capacity compared to WT mice. These results suggest that MYOCD down-regulates GJA1 expression via miR-1 up-regulation, thereby contributing to maintenance of normal sensitivity and development of bladder capacity.
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影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
DOI：
10.1073/pnas.1233635100
发表时间：
2003-08-05
影响因子：
11.1
作者：
Li, SJ;Wang, DZ;Olson, EN
通讯作者：
Olson, EN
影响因子：
5.5
作者：
McHale, N;Hollywood, M;Thornbury, K
通讯作者：
Thornbury, K
影响因子：
15.9
作者：
Huang, Jianhe;Cheng, Lan;Parmacek, Michael S.
通讯作者：
Parmacek, Michael S.
DOI：
10.1161/atvbaha.110.218149
发表时间：
2011-02
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Chen J;Yin H;Jiang Y;Radhakrishnan SK;Huang ZP;Li J;Shi Z;Kilsdonk EP;Gui Y;Wang DZ;Zheng XL
通讯作者：
Zheng XL