Myocardin and microRNA-1 modulate bladder activity through connexin 43 expression during post-natal development

Masaaki Imamura, Yoshio Sugino, Xiaochun Long, Orazio J. Slivano, Nobuyuki Nishikawa, Naoki Yoshimura, Joseph M. Miano

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1819-1826
Number of pages8
JournalJournal of Cellular Physiology
Volume228
Issue number9
DOIs
StatePublished - Sep 1 2013
Externally publishedYes

Fingerprint

Connexin 43
MicroRNAs
Urinary Bladder
Muscle
Smooth Muscle Myocytes
Genes
Overactive Urinary Bladder
Gap Junctions
Knockout Mice
Cholinergic Agents
myocardin
Rats
Up-Regulation
Down-Regulation
Maintenance
Cells
Messenger RNA
Molecules
Smooth Muscle
Hypersensitivity

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Imamura, M., Sugino, Y., Long, X., Slivano, O. J., Nishikawa, N., Yoshimura, N., & Miano, J. M. (2013). Myocardin and microRNA-1 modulate bladder activity through connexin 43 expression during post-natal development. Journal of Cellular Physiology, 228(9), 1819-1826. https://doi.org/10.1002/jcp.24333

Myocardin and microRNA-1 modulate bladder activity through connexin 43 expression during post-natal development. / Imamura, Masaaki; Sugino, Yoshio; Long, Xiaochun; Slivano, Orazio J.; Nishikawa, Nobuyuki; Yoshimura, Naoki; Miano, Joseph M.

In: Journal of Cellular Physiology, Vol. 228, No. 9, 01.09.2013, p. 1819-1826.

Research output: Contribution to journalArticle

Imamura, M, Sugino, Y, Long, X, Slivano, OJ, Nishikawa, N, Yoshimura, N & Miano, JM 2013, 'Myocardin and microRNA-1 modulate bladder activity through connexin 43 expression during post-natal development', Journal of Cellular Physiology, vol. 228, no. 9, pp. 1819-1826. https://doi.org/10.1002/jcp.24333
Imamura, Masaaki ; Sugino, Yoshio ; Long, Xiaochun ; Slivano, Orazio J. ; Nishikawa, Nobuyuki ; Yoshimura, Naoki ; Miano, Joseph M. / Myocardin and microRNA-1 modulate bladder activity through connexin 43 expression during post-natal development. In: Journal of Cellular Physiology. 2013 ; Vol. 228, No. 9. pp. 1819-1826.
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