AJOU Central Library Repository: THP-1 세포에서 유로텐신II 억제에 의한 ABCA1 발현 조절 기전

Graduate School of Ajou University Department of Pharmacy 3. Theses(Master)

THP-1 세포에서 유로텐신II 억제에 의한 ABCA1 발현 조절 기전

Alternative Title: Urotensin II blockade recovers ABCA1 expression through ERK/IL-1ß inhibition in human THP-1 cells

Keyword: Atherosclerosis; Urotensin II; Urotensin II receptor; Urotensin II receptor antagonist; Interleukin-1 ß

Alternative Abstract: Urotensin II (UII), the most potent vasoconstrictor peptide identified to date, is expressed at high level in vascular smooth muscle cells (VSMC) and endothelial cells whereas urotensin II receptor (UT) is abundant in monocytes and macrophages of atherosclerotic lesions. UII is highly expressed in the coronary arteries of the atherosclerotic patients compared to normal subjects. Recently, UII was shown to down-regulate ATP binding cassette transporter-A1 (ABCA1) expression, which is responsible for reverse cholesterol transportation in macrophages of atherosclerotic lesions. However, the mechanism was not elucidated clearly. Previous studies revealed that proinflammatory cytokine interleukin-1b (IL-1ß) repressed ABCA1 expression. To further find out the signaling pathway, we investigated whether IL-1ß is associated in UII-induced ABCA1 down-regulation. Our further results provided that UII receptor antagonist (KR-36676) decreased IL-1ß production and significantly recovered ABCA1 expression in mRNA and protein level. UII receptor antagonists was shown to protect atherosclerosis in animal and cell models in previous investigations. Our results implies that UII receptor antagonist (KR-36676) might be possible potent candidate for atherosclerosis by recovering ABCA1 expression via ERK/IL-1ß pathway.

Appears in Collections:: Graduate School of Ajou University > Department of Pharmacy > 3. Theses(Master)

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