Myocardin and MicroRNA-1 Modulate Bladder Activity Through Connexin 43 Expression During Post-natal Development

Overview

Journal J Cell Physiol

Specialties Cell Biology
Physiology

Date 2013 Jan 30

PMID 23359472

Citations 14

Authors

Masaaki Imamura

Yoshio Sugino

Xiaochun Long

Orazio J Slivano

Nobuyuki Nishikawa

Naoki Yoshimura

Joseph M Miano

Affiliations

Soon will be listed here.

Abstract

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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