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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제21권 제1호
- 발행연도
- 2017.1
- 수록면
- 37 - 44 (8page)
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초록· 키워드
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Regulation of vascular smooth muscle cell (VSMC) phenotype plays an essential role in many cardiovascular diseases. In the present study, we provide evidence that kruppel-like factor 8 (KLF8) is essential for tumor necrosis factor α (TNFα)-induced phenotypic conversion of VSMC obtained from thoracic aorta from 4-week-old SD rats. Stimulation of the contractile phenotype of VSMCs with TNFα significantly reduced the VSMC marker gene expression and KLF8. The gene expression of KLF8 was blocked by TNFα stimulation in an ERK-dependent manner.
The promoter region of KLF8 contained putative Sp1, KLF4, and NFκB binding sites. Myocardin significantly enhanced the promoter activity of KLF4 and KLF8.
The ectopic expression of KLF4 strongly enhanced the promoter activity of KLF8.
Moreover, silencing of Akt1 significantly attenuated the promoter activity of KLF8; conversely, the overexpression of Akt1 significantly enhanced the promoter activity of KLF8. The promoter activity of SMA, SM22α, and KLF8 was significantly elevated in the contractile phenotype of VSMCs. The ectopic expression of KLF8 markedly enhanced the expression of SMA and SM22α concomitant with morphological changes. The overexpression of KLF8 stimulated the promoter activity of SMA.
Stimulation of VSMCs with TNFα enhanced the expression of KLF5, and the promoter activity of KLF5 was markedly suppressed by KLF8 ectopic expression. Finally, the overexpression of KLF5 suppressed the promoter activity of SMA and SM22α, thereby reduced the contractility in response to the stimulation of angiotensin II.
These results suggest that cross-regulation of KLF family of transcription factors plays an essential role in the VSMC phenotype.
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등록된 정보가 없습니다.
참고문헌 (41)
참고문헌 신청
Owens GK / 1995 / Regulation of differentiation of vascular smooth muscle cells / Physiol Rev 75:487~517
Wynne BM / 2009 / Vascular smooth muscle cell signaling mechanisms for contraction to angiotensin ii and endothelin-1 / J Am Soc Hypertens 3:84~95
Owens GK / 2004 / Molecular regulation of vascular smooth muscle cell differentiation in development and disease / Physiol Rev 84:767~801
McConnell BB / 2010 / Mammalian Krüppel-like factors in health and diseases / Physiol Rev 90:1337~1381
Haldar SM / 2007 / Kruppel-like factors (KLFs) in muscle biology / J Mol Cell Cardiol 43:1~10
Wynne BM / 2009 / Vascular smooth muscle cell signaling mechanisms for contraction to angiotensin ii and endothelin-1 / J Am Soc Hypertens 3:84~95
Owens GK / 2004 / Molecular regulation of vascular smooth muscle cell differentiation in development and disease / Physiol Rev 84:767~801
McConnell BB / 2010 / Mammalian Krüppel-like factors in health and diseases / Physiol Rev 90:1337~1381
Haldar SM / 2007 / Kruppel-like factors (KLFs) in muscle biology / J Mol Cell Cardiol 43:1~10
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