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MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo
Takahiro Horie, Koh Ono, Masahito Horiguchi, Hitoo Nishi, Tomoyuki Nakamura, Kazuya Nagao, Minako Kinoshita, Yasuhide Kuwabara, Hiroyuki Marusawa, Yoshitaka Iwanaga, Koji Hasegawa, Masayuki Yokode, Takeshi Kimura and Toru Kita
Proceedings of the National Academy of Sciences of the United States of America
Vol. 107, No. 40 (October 5, 2010), pp. 17321-17326
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/20779961
Page Count: 6
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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 A 1 (ABCA 1) 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 ABCA 1 levels and higher apoA-I—dependent cholesterol efflux than those from WT mice. ABCA 1 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 ABCA 1 expression and HDL biogenesis in vivo.
Proceedings of the National Academy of Sciences of the United States of America © 2010 National Academy of Sciences