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Induction of angiotensin converting enzyme after miR-143/145 deletion is critical for impaired smooth muscle contractility.

Dahan, Diana LU ; Ekman, Mari LU ; Larsson Callerfelt, Anna-Karin LU ; Turczynska, Karolina LU ; Boettger, Thomas; Braun, Thomas; Swärd, Karl LU and Albinsson, Sebastian LU (2014) In American Journal of Physiology: Cell Physiology 307(12). p.1093-1101
Abstract
MicroRNAs have emerged as regulators of smooth muscle cell phenotype with a role in smooth muscle-related disease. Studies have shown that miR-143 and miR-145 are the most highly expressed microRNAs in smooth muscle cells, controlling differentiation and function. The effect of miR-143/145 knockout has been established in the vasculature but not in smooth muscle from other organs. Using knockout mice we found that maximal contraction induced by either depolarization or phosphatase inhibition was reduced in vascular and airway smooth muscle but maintained in the urinary bladder. Furthermore, a reduction of media thickness and reduced expression of differentiation markers was seen in the aorta but not in the bladder. Supporting the view that... (More)
MicroRNAs have emerged as regulators of smooth muscle cell phenotype with a role in smooth muscle-related disease. Studies have shown that miR-143 and miR-145 are the most highly expressed microRNAs in smooth muscle cells, controlling differentiation and function. The effect of miR-143/145 knockout has been established in the vasculature but not in smooth muscle from other organs. Using knockout mice we found that maximal contraction induced by either depolarization or phosphatase inhibition was reduced in vascular and airway smooth muscle but maintained in the urinary bladder. Furthermore, a reduction of media thickness and reduced expression of differentiation markers was seen in the aorta but not in the bladder. Supporting the view that phenotype switching depends on a tissue-specific target of miR-143/145, we found induction of angiotensin converting enzyme in the aorta but not in the bladder where angiotensin converting enzyme was expressed at a low level. Chronic treatment with angiotensin type-1 receptor antagonist restored contractility in miR-143/145-deficient aorta while leaving bladder contractility unaffected. This shows that tissue-specific targets are critical for the effects of miR-143/145 on smooth muscle differentiation and that angiotensin converting enzyme is one such target. (Less)
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Contribution to journal
publication status
published
subject
in
American Journal of Physiology: Cell Physiology
volume
307
issue
12
pages
1093 - 1101
publisher
American Physiological Society
external identifiers
  • pmid:25273883
  • wos:000346473400004
  • scopus:84918778428
ISSN
1522-1563
DOI
10.1152/ajpcell.00250.2014
language
English
LU publication?
yes
id
831feed0-c5ea-4af4-bf03-f0e4d6d77205 (old id 4738574)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25273883?dopt=Abstract
date added to LUP
2014-11-04 19:53:43
date last changed
2017-09-17 04:05:12
@article{831feed0-c5ea-4af4-bf03-f0e4d6d77205,
  abstract     = {MicroRNAs have emerged as regulators of smooth muscle cell phenotype with a role in smooth muscle-related disease. Studies have shown that miR-143 and miR-145 are the most highly expressed microRNAs in smooth muscle cells, controlling differentiation and function. The effect of miR-143/145 knockout has been established in the vasculature but not in smooth muscle from other organs. Using knockout mice we found that maximal contraction induced by either depolarization or phosphatase inhibition was reduced in vascular and airway smooth muscle but maintained in the urinary bladder. Furthermore, a reduction of media thickness and reduced expression of differentiation markers was seen in the aorta but not in the bladder. Supporting the view that phenotype switching depends on a tissue-specific target of miR-143/145, we found induction of angiotensin converting enzyme in the aorta but not in the bladder where angiotensin converting enzyme was expressed at a low level. Chronic treatment with angiotensin type-1 receptor antagonist restored contractility in miR-143/145-deficient aorta while leaving bladder contractility unaffected. This shows that tissue-specific targets are critical for the effects of miR-143/145 on smooth muscle differentiation and that angiotensin converting enzyme is one such target.},
  author       = {Dahan, Diana and Ekman, Mari and Larsson Callerfelt, Anna-Karin and Turczynska, Karolina and Boettger, Thomas and Braun, Thomas and Swärd, Karl and Albinsson, Sebastian},
  issn         = {1522-1563},
  language     = {eng},
  number       = {12},
  pages        = {1093--1101},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Cell Physiology},
  title        = {Induction of angiotensin converting enzyme after miR-143/145 deletion is critical for impaired smooth muscle contractility.},
  url          = {http://dx.doi.org/10.1152/ajpcell.00250.2014},
  volume       = {307},
  year         = {2014},
}