Deletion of dicer in smooth muscle affects voiding pattern and reduces detrusor contractility and neuroeffector transmission.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2609118
- author
- Sadegh, Mardjaneh Karbalaei ; Ekman, Mari ; Rippe, Catarina LU ; Uvelius, Bengt LU ; Swärd, Karl LU and Albinsson, Sebastian LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 7
- issue
- 4
- article number
- e35882
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000305336000073
- pmid:22558254
- scopus:84860464993
- pmid:22558254
- 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
- 2016-04-01 14:15:06
- date last changed
- 2022-01-27 23:34:28
@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.}},
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 (PLoS)}},
series = {{PLoS ONE}},
title = {{Deletion of dicer in smooth muscle affects voiding pattern and reduces detrusor contractility and neuroeffector transmission.}},
url = {{https://lup.lub.lu.se/search/files/3868051/3125973.pdf}},
doi = {{10.1371/journal.pone.0035882}},
volume = {{7}},
year = {{2012}},
}