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KMID : 1036020210100010099
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지질.동맥경화학회지
2021 Volume.10 No. 1 p.99 ~ p.110
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Modulation of Vascular Smooth Muscle Cell Phenotype by High Mobility Group AT-Hook 1
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Jung Yoo-Jin
Lee Hae-Sun
Ha Jung-Min
Jin Seo-Yeon
Kum Hye-Jin
Vafaeinik Farzaneh
Ha Hong-Koo
Song Sang-Heon
Kim Chi-Dae
Bae Sun-Sik
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Abstract
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Objective: The purpose of this study is to examine the effect of high mobility group AT-hook 1 (HMGA1) on the phenotyptic change of vascular smooth muscle cells (VSMCs).
Methods: Gene silencing and overexpression of HMGA1 were introduced to evaluate the effect of HMGA1 expression on the phenotypic change of VSMCs. Marker gene expression of VSMCs was measured by promoter assay, quantitative polymerase chain reaction, and western blot analysis. Common left carotid artery ligation model was used to establish in vivo neointima formation.
Results: HMGA1 was expressed strongly in the synthetic type of VSMCs and significantly downregulated during the differentiation of VSMCs. Silencing of HMGA1 in the synthetic type of VSMCs enhanced the expression of contractile marker genes thereby enhanced angiotensin II (Ang II)-dependent contraction, however, significantly suppressed proliferation and migration. Stimulation of contractile VSMCs with platelet-derived growth factor (PDGF) enhanced HMGA1 expression concomitant with the downregulation of marker gene expression which was blocked significantly by the silencing of HMGA1. Silencing of HMGA1 retained the Ang II-dependent contractile function, which was curtailed by PDGF stimulation, however, overexpression of HMGA1 in the contractile type of VSMCs suppressed marker gene expression. Proliferation and migration were enhanced significantly by the overexpression of HMGA1. Furthermore, the Ang II-dependent contraction was reduced significantly by the overexpression of HMGA1. Finally, the expression of HMGA1 was enhanced significantly in the ligated artery, especially in the neointima area.
Conclusion: HMGA1 plays an essential role in the phenotypic modulation of VSMCs. Therefore, paracrine factors such as PDGF may affect vascular remodeling through the regulation of HMGA1.
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KEYWORD
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HMGA, Smooth muscle, Phenotype, Cell proliferation, Platelet-derived growth factor
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