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


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.
Laboratory Medical College, Jilin Medical College, Jilin, P.R.China E-mail : jiangyongpost@sina.com.
Yong
Y
Jiang
D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology*; D017209:Apoptosis; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005263:Femoral Artery / Q000293:injuries / Q000473:pathology*; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000293:injuries / Q000473:pathology*; D058426:Neointima / Q000209:etiology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology*; D066253:Vascular Remodeling; D014945:Wound Healing
D001057:Apolipoproteins E; C496021:Aqp1 protein, mouse; C511173:Mrtfa protein, mouse; D012333:RNA, Messenger; D015534:Trans-Activators; D051398:Aquaporin 1