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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
- 2021.1
- 수록면
- 221 - 226 (6page)
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초록· 키워드
오류제보하기
Hepcidin (HAMP) is synthesized in the liver. It is a key ironregulatory hormone that controls systemic iron homeostasis. Cereblon (CRBN) and Kruppel-like factor 15 (KLF15) are known to regulate diverse physiological functions. In this study, we investigated the role of CRBN on hepatic hepcidin gene expression and production under gluconeogenic stimuli. Fasted mice as well as forskolin (FSK)- and glucagon (GLU)-treated mice had reduced serum iron levels but increased expression levels of hepatic Crbn and Klf15 and hepcidin secretion. MicroRNA (miRNA) expression analysis of fasted and Ad-Crbninfected mice revealed significant reduction of microRNA-639 (miR-639). Hepatic overexpression of Crbn elevated hepcidin expression and production along with Klf15 gene expression, whereas knockdown of Crbn and Klf15 markedly decreased FSK- and fasting-mediated induction of hepcidin gene expression and its biosynthesis in mouse livers and primary hepatocytes. Moreover, expression of KLF15 significantly increased the activity of hepcidin reporter gene. It was exclusively dependent on the KLF15-binding site identified within the hepcidin gene promoter. Overall, this study demonstrates that CRBN and KLF15 are novel mediators of gluconeogenic signal-induced hepcidin gene expression and production. Thus, CRBN and KLF15 might be novel potential therapeutic targets to intervene metabolic dysfunction.
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등록된 정보가 없습니다.
참고문헌 (31)
참고문헌 신청
Anderson ER / 2013 / Iron homeostasis in the liver / Compr Physiol 3:315~330
Zumerle S / 2014 / Targeted disruption of hepcidin in the liver recapitulates the hemochromatotic phenotype / Blood 123:3646~3650
Lesbordes-Brion JC / 2006 / Targeted disruption of the hepcidin 1 gene results in severe hemochromatosis / Blood 108:1402~1405
Deschemin JC / 2017 / Pulmonary iron homeostasis in hepcidin knockout mice / Front Physiol 8:804
Viatte L / 2005 / Deregulation of proteins involved in iron metabolism in hepcidin-deficient mice / Blood 105:4861~4864
Zumerle S / 2014 / Targeted disruption of hepcidin in the liver recapitulates the hemochromatotic phenotype / Blood 123:3646~3650
Lesbordes-Brion JC / 2006 / Targeted disruption of the hepcidin 1 gene results in severe hemochromatosis / Blood 108:1402~1405
Deschemin JC / 2017 / Pulmonary iron homeostasis in hepcidin knockout mice / Front Physiol 8:804
Viatte L / 2005 / Deregulation of proteins involved in iron metabolism in hepcidin-deficient mice / Blood 105:4861~4864
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