This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: [10.1002/jcp.24333].
Original Research Article
Myocardin and MicroRNA-1 modulate bladder activity through connexin 43 expression during post-natal development†
Copyright © 2013 Wiley Periodicals, Inc.
- Accepted manuscript online: 28 JAN 2013 08:47AM EST
- Manuscript Accepted: 18 JAN 2013
- Manuscript Revised: 14 DEC 2012
- Manuscript Received: 31 MAY 2012
- NIH. Grant Numbers: HL62572, HL091168
- SUMITOMO Life Social Welfare Services Foundation
- smooth muscle;
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 mouse bladders showed normal development from early postnatal 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 wild type 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. J. Cell. Physiol. © 2013 Wiley Periodicals, Inc.