MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo

被引：320

作者：

Horie, Takahiro ^{[1
,2
]}

Ono, Koh ^{[1
]}

Horiguchi, Masahito ^{[1
]}

Nishi, Hitoo ^{[1
]}

Nakamura, Tomoyuki ^{[3
]}

Nagao, Kazuya ^{[1
]}

Kinoshita, Minako ^{[1
]}

Kuwabara, Yasuhide ^{[1
]}

Marusawa, Hiroyuki ^{[4
]}

Iwanaga, Yoshitaka ^{[5
]}

Hasegawa, Koji ^{[7
]}

Yokode, Masayuki ^{[2
]}

Kimura, Takeshi ^{[1
]}

Kita, Toru ^{[6
]}

机构：

[1] Kyoto Univ, Grad Sch Med, Dept Cardiovasc Med, Kyoto 6068507, Japan

[2] Kyoto Univ, Grad Sch Med, Translat Res Ctr, Dept Clin Innovat Med, Kyoto 6068507, Japan

[3] Kansai Med Univ, Dept Pharmacol, Osaka 5708506, Japan

[4] Kyoto Univ, Grad Sch Med, Dept Gastrointestinal Med, Kyoto 6068507, Japan

[5] Kinki Univ, Sch Med, Dept Internal Med, Div Cardiol, Osaka 5898511, Japan

[6] Kobe City Gen Hosp, Dept Cardiovasc Med, Kobe, Hyogo 6500046, Japan

[7] Kyoto Med Ctr, Clin Res Inst, Div Translat Res, Kyoto 6128555, Japan

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2010年 / 107卷 / 40期

基金：

日本学术振兴会;

关键词：

ABCA1; macrophage; cholesterol efflux; liver; metabolic syndrome; DENSITY-LIPOPROTEIN DEFICIENCY; REVERSE CHOLESTEROL TRANSPORT; FATTY-ACID SYNTHESIS; TANGIER-DISEASE; TRANSGENIC MICE; HOST GENES; EFFLUX; LIVER; TRANSCRIPTION; HOMEOSTASIS;

D O I：

10.1073/pnas.1008499107

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Sterol regulatory element-binding protein 2 (SREBP-2) transcription factor has been identified as a key protein in cholesterol metabolism through the transactivation of the LDL receptor and cholesterol biosynthesis genes. Here, we generated mice lacking microRNA (miR)-33, encoded by an intron of the Srebp2, and showed that miR-33 repressed the expression of ATP-binding cassette transporter A1 (ABCA1) protein, a key regulator of HDL synthesis by mediating cholesterol efflux from cells to apolipoprotein A (apoA)-I. In fact, peritoneal macrophages derived from miR-33-deficient mice showed a marked increase in ABCA1 levels and higher apoA-I-dependent cholesterol efflux than those from WT mice. ABCA1 protein levels in liver were also higher in miR-33-deficient mice than in WT mice. Moreover, miR-33-deficient mice had significantly higher serum HDL cholesterol levels than WT mice. These data establish a critical role for miR-33 in the regulation of ABCA1 expression and HDL biogenesis in vivo.

引用

页码：17321 / 17326

页数：6

共 38 条

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