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MicroRNA MiR-199a-5p Regulates Smooth Muscle Cell Proliferation and Morphology by Targeting WNT2 Signaling Pathway.

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Title: MicroRNA MiR-199a-5p Regulates Smooth Muscle Cell Proliferation and Morphology by Targeting WNT2 Signaling Pathway.
Authors: Gheinani, Ali Hashemi1, Burkhard, Fiona C.2, Rehrauer, Hubert3, Aquino Fournier, Catharine3, Monastyrskaya, Katia1 monastyk@dkf.unibe.ch
Source: Journal of Biological Chemistry. 3/13/2015, Vol. 290 Issue 11, p7067-7086. 20p.
Subjects: MicroRNA, Interstitial cystitis, Cell cycle regulation, Cytoskeleton, Smooth muscle, Wnt proteins, Cell proliferation, Physiology, Disease risk factors
Abstract: MicroRNA miR-199a-5p impairs tight junction formation, leading to increased urothelial permeability in bladder pain syndrome. Now, using transcriptome analysis in urothelial TEU-2 cells, we implicate it in the regulation of cell cycle, cytoskeleton remodeling, TGF, and WNT signaling pathways. MiR-199a-5p is highly expressed in the smooth muscle layer of the bladder, and we altered its levels in bladder smooth muscle cells (SMCs) to validate the pathway analysis. Inhibition of miR-199a-5p with antimiR increased SMC proliferation, reduced cell size, and up-regulated miR-199a-5p targets, including WNT2. Overexpression of WNT2 protein or treating SMCs with recombinant WNT2 closely mimicked the miR-199a-5p inhibition, whereas down-regulation of WNT2 in antimiR-expressing SMCs with shRNA restored cell phenotype and proliferation rates. Overexpression of miR-199a-5p in the bladder SMCs significantly increased cell size and up-regulated SM22, SM_-actin, and SM myosin heavy chain mRNA and protein levels. These changes as well as increased expression of ACTG2, TGFB1I1, and CDKN1A were mediated by up-regulation of the smooth muscle-specific transcriptional activator myocardin at mRNA and protein levels. Myocardin-related transcription factor A downstream targets Id3 and MYL9 were also induced. Up-regulation of myocardin was accompanied by down-regulation of WNT-dependent inhibitory Krüppel-like transcription factor 4 in miR-199a-5poverexpressing cells. In contrast, Krüppel-like transcription factor 4 was induced in antimiR-expressing cells following the activation of WNT2 signaling, leading to repression of myocardin-dependent genes. MiR-199a-5p plays a critical role in the WNT2-mediated regulation of proliferative and differentiation processes in the smooth muscle and may behave as a key modulator of smooth muscle hypertrophy, which is relevant for organ remodeling. [ABSTRACT FROM AUTHOR]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Label: Title
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  Data: MicroRNA MiR-199a-5p Regulates Smooth Muscle Cell Proliferation and Morphology by Targeting WNT2 Signaling Pathway.
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  Data: <searchLink fieldCode="AR" term="%22Gheinani%2C+Ali+Hashemi%22">Gheinani, Ali Hashemi</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Burkhard%2C+Fiona+C%2E%22">Burkhard, Fiona C.</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Rehrauer%2C+Hubert%22">Rehrauer, Hubert</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Aquino+Fournier%2C+Catharine%22">Aquino Fournier, Catharine</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Monastyrskaya%2C+Katia%22">Monastyrskaya, Katia</searchLink><relatesTo>1</relatesTo><i> monastyk@dkf.unibe.ch</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 3/13/2015, Vol. 290 Issue 11, p7067-7086. 20p.
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  Data: <searchLink fieldCode="DE" term="%22MicroRNA%22">MicroRNA</searchLink><br /><searchLink fieldCode="DE" term="%22Interstitial+cystitis%22">Interstitial cystitis</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+cycle+regulation%22">Cell cycle regulation</searchLink><br /><searchLink fieldCode="DE" term="%22Cytoskeleton%22">Cytoskeleton</searchLink><br /><searchLink fieldCode="DE" term="%22Smooth+muscle%22">Smooth muscle</searchLink><br /><searchLink fieldCode="DE" term="%22Wnt+proteins%22">Wnt proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+proliferation%22">Cell proliferation</searchLink><br /><searchLink fieldCode="DE" term="%22Physiology%22">Physiology</searchLink><br /><searchLink fieldCode="DE" term="%22Disease+risk+factors%22">Disease risk factors</searchLink>
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  Label: Abstract
  Group: Ab
  Data: MicroRNA miR-199a-5p impairs tight junction formation, leading to increased urothelial permeability in bladder pain syndrome. Now, using transcriptome analysis in urothelial TEU-2 cells, we implicate it in the regulation of cell cycle, cytoskeleton remodeling, TGF, and WNT signaling pathways. MiR-199a-5p is highly expressed in the smooth muscle layer of the bladder, and we altered its levels in bladder smooth muscle cells (SMCs) to validate the pathway analysis. Inhibition of miR-199a-5p with antimiR increased SMC proliferation, reduced cell size, and up-regulated miR-199a-5p targets, including WNT2. Overexpression of WNT2 protein or treating SMCs with recombinant WNT2 closely mimicked the miR-199a-5p inhibition, whereas down-regulation of WNT2 in antimiR-expressing SMCs with shRNA restored cell phenotype and proliferation rates. Overexpression of miR-199a-5p in the bladder SMCs significantly increased cell size and up-regulated SM22, SM_-actin, and SM myosin heavy chain mRNA and protein levels. These changes as well as increased expression of ACTG2, TGFB1I1, and CDKN1A were mediated by up-regulation of the smooth muscle-specific transcriptional activator myocardin at mRNA and protein levels. Myocardin-related transcription factor A downstream targets Id3 and MYL9 were also induced. Up-regulation of myocardin was accompanied by down-regulation of WNT-dependent inhibitory Krüppel-like transcription factor 4 in miR-199a-5poverexpressing cells. In contrast, Krüppel-like transcription factor 4 was induced in antimiR-expressing cells following the activation of WNT2 signaling, leading to repression of myocardin-dependent genes. MiR-199a-5p plays a critical role in the WNT2-mediated regulation of proliferative and differentiation processes in the smooth muscle and may behave as a key modulator of smooth muscle hypertrophy, which is relevant for organ remodeling. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1074/jbc.M114.618694
    Languages:
      – Code: eng
        Text: English
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      Pagination:
        PageCount: 20
        StartPage: 7067
    Subjects:
      – SubjectFull: MicroRNA
        Type: general
      – SubjectFull: Interstitial cystitis
        Type: general
      – SubjectFull: Cell cycle regulation
        Type: general
      – SubjectFull: Cytoskeleton
        Type: general
      – SubjectFull: Smooth muscle
        Type: general
      – SubjectFull: Wnt proteins
        Type: general
      – SubjectFull: Cell proliferation
        Type: general
      – SubjectFull: Physiology
        Type: general
      – SubjectFull: Disease risk factors
        Type: general
    Titles:
      – TitleFull: MicroRNA MiR-199a-5p Regulates Smooth Muscle Cell Proliferation and Morphology by Targeting WNT2 Signaling Pathway.
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            NameFull: Gheinani, Ali Hashemi
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            NameFull: Burkhard, Fiona C.
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            NameFull: Rehrauer, Hubert
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            NameFull: Aquino Fournier, Catharine
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            NameFull: Monastyrskaya, Katia
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            – D: 13
              M: 03
              Text: 3/13/2015
              Type: published
              Y: 2015
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              Value: 290
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              Value: 11
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