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Deletion of dicer in smooth muscle affects voiding pattern and reduces detrusor contractility and neuroeffector transmission.

Sadegh, Mardjaneh Karbalaei; Ekman, Mari; Rippe, Catarina LU ; Uvelius, Bengt LU ; Swärd, Karl LU and Albinsson, Sebastian LU (2012) In PLoS ONE 7(4).
Abstract
MicroRNAs have emerged as important regulators of smooth muscle phenotype and may play important roles in pathogenesis of various smooth muscle related disease states. The aim of this study was to investigate the role of miRNAs for urinary bladder function. We used an inducible and smooth muscle specific Dicer knockout (KO) mouse which resulted in significantly reduced levels of miRNAs, including miR-145, miR-143, miR-22, miR125b-5p and miR-27a, from detrusor preparations without mucosa. Deletion of Dicer resulted in a disturbed micturition pattern in vivo and reduced depolarization-induced pressure development in the isolated detrusor. Furthermore, electrical field stimulation revealed a decreased cholinergic but maintained purinergic... (More)
MicroRNAs have emerged as important regulators of smooth muscle phenotype and may play important roles in pathogenesis of various smooth muscle related disease states. The aim of this study was to investigate the role of miRNAs for urinary bladder function. We used an inducible and smooth muscle specific Dicer knockout (KO) mouse which resulted in significantly reduced levels of miRNAs, including miR-145, miR-143, miR-22, miR125b-5p and miR-27a, from detrusor preparations without mucosa. Deletion of Dicer resulted in a disturbed micturition pattern in vivo and reduced depolarization-induced pressure development in the isolated detrusor. Furthermore, electrical field stimulation revealed a decreased cholinergic but maintained purinergic component of neurogenic activation in Dicer KO bladder strips. The ultrastructure of detrusor smooth muscle cells was well maintained, and the density of nerve terminals was similar. Western blotting demonstrated reduced contents of calponin and desmin. Smooth muscle α-actin, SM22α and myocardin were unchanged. Activation of strips with exogenous agonists showed that depolarization-induced contraction was preferentially reduced; ATP- and calyculin A-induced contractions were unchanged. Quantitative real time PCR and western blotting demonstrated reduced expression of Cav1.2 (Cacna1c). It is concluded that smooth muscle miRNAs play an important role for detrusor contractility and voiding pattern of unrestrained mice. This is mediated in part via effects on expression of smooth muscle differentiation markers and L-type Ca(2+) channels in the detrusor. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
7
issue
4
publisher
Public Library of Science
external identifiers
  • wos:000305336000073
  • pmid:22558254
  • scopus:84860464993
ISSN
1932-6203
DOI
10.1371/journal.pone.0035882
language
English
LU publication?
yes
id
acf7e6cd-0d4b-4786-ba1f-8d6867717ab4 (old id 2609118)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22558254?dopt=Abstract
date added to LUP
2012-06-02 15:59:42
date last changed
2017-05-28 04:06:12
@article{acf7e6cd-0d4b-4786-ba1f-8d6867717ab4,
  abstract     = {MicroRNAs have emerged as important regulators of smooth muscle phenotype and may play important roles in pathogenesis of various smooth muscle related disease states. The aim of this study was to investigate the role of miRNAs for urinary bladder function. We used an inducible and smooth muscle specific Dicer knockout (KO) mouse which resulted in significantly reduced levels of miRNAs, including miR-145, miR-143, miR-22, miR125b-5p and miR-27a, from detrusor preparations without mucosa. Deletion of Dicer resulted in a disturbed micturition pattern in vivo and reduced depolarization-induced pressure development in the isolated detrusor. Furthermore, electrical field stimulation revealed a decreased cholinergic but maintained purinergic component of neurogenic activation in Dicer KO bladder strips. The ultrastructure of detrusor smooth muscle cells was well maintained, and the density of nerve terminals was similar. Western blotting demonstrated reduced contents of calponin and desmin. Smooth muscle α-actin, SM22α and myocardin were unchanged. Activation of strips with exogenous agonists showed that depolarization-induced contraction was preferentially reduced; ATP- and calyculin A-induced contractions were unchanged. Quantitative real time PCR and western blotting demonstrated reduced expression of Cav1.2 (Cacna1c). It is concluded that smooth muscle miRNAs play an important role for detrusor contractility and voiding pattern of unrestrained mice. This is mediated in part via effects on expression of smooth muscle differentiation markers and L-type Ca(2+) channels in the detrusor.},
  articleno    = {e35882},
  author       = {Sadegh, Mardjaneh Karbalaei and Ekman, Mari and Rippe, Catarina and Uvelius, Bengt and Swärd, Karl and Albinsson, Sebastian},
  issn         = {1932-6203},
  language     = {eng},
  number       = {4},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Deletion of dicer in smooth muscle affects voiding pattern and reduces detrusor contractility and neuroeffector transmission.},
  url          = {http://dx.doi.org/10.1371/journal.pone.0035882},
  volume       = {7},
  year         = {2012},
}