MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein 2 (Srebp2) regulates HDL in vivo.
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.
Horie
Takahiro
T
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Ono
Koh
K
Horiguchi
Masahito
M
Nishi
Hitoo
H
Nakamura
Tomoyuki
T
Nagao
Kazuya
K
Kinoshita
Minako
M
Kuwabara
Yasuhide
Y
Marusawa
Hiroyuki
H
Iwanaga
Yoshitaka
Y
Hasegawa
Koji
K
Yokode
Masayuki
M
Kimura
Takeshi
T
Kita
Toru
T
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002460:Cell Line; D002645:Chickens; D008076:Cholesterol, HDL / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007438:Introns; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D051782:Sterol Regulatory Element Binding Protein 2 / Q000235:genetics* / Q000378:metabolism
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL; D035683:MicroRNAs; D051782:Sterol Regulatory Element Binding Protein 2