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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 613 - 624 (12page)
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Background and Objectives: Vascular smooth muscle cell (SMC) proliferation and migration play a critical role in neointimal formation. Focal adhesion is involved in cell proliferation and migration, and talin is known to be a key regulator of these processes. We synthesized a new talin modulator that binds to the talin protein, and investigated its effects on SMCs and neointimal formation after vascular injury. Methods: Human aortic SMCs (HAoSMCs) were treated with a newly synthesized talin modulator. Apolipoprotein E knockout (ApoE KO) mice were subjected to left femoral arterial injury and orally administered with the talin modulator daily. Laser Doppler imager was used to compare the blood flow, and injured femoral arteries and blood serum were analyzed after 28 days. Results: The talin modulator significantly inhibited cell proliferation in a concentration-dependent manner and suppressed the migration of HAoSMCs. Treatment with a talin modulator resulted in a significant reduction in the phosphorylation of focal adhesion molecules and downstream signaling molecules related to cell proliferation and migration. The effects of the talin modulator in HAoSMCs were found to be reversible, as evidenced by the reactivation of signaling pathways upon its removal. After 28 days of administration of the talin modulator, an improvement in the blood flow and reduction in neointimal formation in the injured femoral arteries were observed. Conclusions: We demonstrated the inhibitory effects of a talin modulator on SMC proliferation and migration, and that were associated with downregulation of signaling pathways, resulting in the attenuation of neointimal formation in ApoE KO mice.
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참고문헌 (23)
참고문헌 신청
Bennett MR / 2016 / Vascular smooth muscle cells in atherosclerosis / Circ Res 118:692~702
Kim JH / 2019 / Fimasartan reduces neointimal formation and inflammation after carotid arterial injury in apolipoprotein E knockout mice / Mol Med 25:33
Nagayama K / 2015 / Exendin-4 prevents vascular smooth muscle cell proliferation and migration by angiotensin II via the inhibition of ERK1/2 and JNK signaling pathways / PLoS One 10:e0137960
Huttenlocher A / 2011 / Integrins in cell migration / Cold Spring Harb Perspect Biol 3:a005074
Wozniak MA / 2004 / Focal adhesion regulation of cell behavior / Biochim Biophys Acta 1692:103~119
Kim JH / 2019 / Fimasartan reduces neointimal formation and inflammation after carotid arterial injury in apolipoprotein E knockout mice / Mol Med 25:33
Nagayama K / 2015 / Exendin-4 prevents vascular smooth muscle cell proliferation and migration by angiotensin II via the inhibition of ERK1/2 and JNK signaling pathways / PLoS One 10:e0137960
Huttenlocher A / 2011 / Integrins in cell migration / Cold Spring Harb Perspect Biol 3:a005074
Wozniak MA / 2004 / Focal adhesion regulation of cell behavior / Biochim Biophys Acta 1692:103~119
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