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The expression of MRTF-A and AQP1 play important roles in the pathological vascular remodeling.

AbstractBACKGROUND:
Objective Myocardin-related transcription factor (MRTF)-A is a Rho signaling-responsive co-activator of serum response factor (SRF). The purpose of this study is to investigate the role of MRTF-A and AQP1 (aquaporin 1) in pathological vascular remodeling.
MATERIALS AND METHODS:
MRTF-A, AQP1 and neointima expression was detected both in the wire injured femoral arteries of wild-type mice and the atherosclerotic aortic tissues of ApoE-/- mice. Expression of ICAM-1, matrix metallopeptidase 9 (MMP-9) and integrin β1 were also assayed. The intercourse relationship between the molecules were investigated by interfering RNA and inhibitor assay.
RESULTS:
MRTF-A and AQP1 expression were significantly higher in the wire injured femoral arteries of wild-type mice and in the atherosclerotic aortic tissues of ApoE-/- mice than in healthy control tissues. Both in wire-injured femoral arteries in MRTF-A knockout (Mkl1-/-) mice and atherosclerotic lesions in Mkl1-/-; ApoE-/- mice, neointima formation were significantly attenuated and the expression of AQP1 were significantly decreased. Expression of ICAM-1, matrix metallopeptidase 9 (MMP-9) and integrin β1, three SRF targets and key regulators of cell migration, and AQP1 in injured arteries was significantly weaker in Mkl1-/- mice than in wild-type mice. In cultured vascular smooth muscle cells (VSMCs), knocking down MRTF-A reduced expression of these genes and significantly impaired cell migration. Underlying the increased MRTF-A expression in dedifferentiated VSMCs were the down-regulation of microRNA-300. Moreover, the MRTF-A inhibitor CCG1423 significantly reduced neointima formation following wire injury in mice.
CONCLUSIONS:
MRTF-A could be a novel therapeutic target for the treatment of vascular diseases.
AuthorsYong Jiang
JournalAsian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 16 Issue 4 Pg. 1375-83 ( 2015) ISSN: 2476-762X [Electronic] Thailand
PMID25743802 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)
Chemical References
  • Apolipoproteins E
  • Aqp1 protein, mouse
  • Mrtfa protein, mouse
  • RNA, Messenger
  • Trans-Activators
  • Aquaporin 1
Topics
  • Animals
  • Apolipoproteins E (physiology)
  • Apoptosis
  • Aquaporin 1 (genetics, metabolism)
  • Atherosclerosis (etiology, pathology)
  • Blotting, Western
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Femoral Artery (injuries, pathology)
  • Immunoprecipitation
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular (injuries, pathology)
  • Neointima (etiology, pathology)
  • RNA, Messenger (genetics)
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Trans-Activators (physiology)
  • Vascular Remodeling
  • Wound Healing

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