system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: ATP Binding Cassette Transporter 1, Animals, Binding Sites, Carnitine O-Palmitoyltransferase, Cell Line, Tumor, Cholesterol, Gene Expression Regulation, Humans, Intracellular Signaling Peptides and Proteins, Introns, Isoxazoles, Liver, Male, Membrane Proteins, Mice, Inbred C57BL, Mice, Knockout, MicroRNAs, Promoter Regions, Genetic, Quinolines, RNA, Messenger, Receptors, Cytoplasmic and Nuclear, Sterol Regulatory Element Binding Protein 2, Transcription, Genetic, Transfection.
user
Does the nuclear receptor FXR uncouple the actions of miR-33 from SREBP-2? Context: To determine whether activation of farnesoid X receptor (FXR) alters cellular and plasma cholesterol homeostasis as a result of regulation of Srebp-2 and miR-33. Chromatin immunoprecipitation sequencing data identified an FXR response element within intron 10 of the Srebp-2 gene. Consistent with this observation, treatment of mice with FXR-specific agonists (GSK2324 or GW4064) rapidly increased hepatic levels of Srebp-2 mRNA, precursor sterol response element binding protein 2 (pSREBP-2) protein, and miR-33. Furthermore, miR-33 targets, that include ABCA1 (ATP binding cassette transporter A1), NSF (N-ethylmaleimide-sensitive factor), and CPT1 (carnitine palmitoyltransferase 1), were all reduced in GSK2324-treated mice. In contrast, neither nuclear SREBP-2 protein (nSREBP-2) nor SREBP-2 target genes were induced after FXR activation. The inability to process pSREBP-2 to nSREBP-2 is likely a consequence of the induction of insulin INSIG-2A (induced gene 2A) by FXR agonists. Finally, we show that FXR-dependent induction of both Srebp-2 and miR-33 is ablated in Scap(-/-) mice that lack nuclear SREBP-2.
assistant
We demonstrate that the activation of FXR uncouples the expression of nuclear SREBP-2 and miR-33, and the regulation of their respective target genes. Further, we conclude that the FXR agonist-dependent increase in miR-33 requires transcription of the Srebp-2 gene. Final Decision: yes