دورية أكاديمية
Multi-step regulation of microRNA expression and secretion into small extracellular vesicles by insulin.
| العنوان: | Multi-step regulation of microRNA expression and secretion into small extracellular vesicles by insulin. |
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| المؤلفون: | Lino M; Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA; Harvard Medical School, Harvard University, Boston, MA, USA., Garcia-Martin R; Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA; Harvard Medical School, Harvard University, Boston, MA, USA., Muñoz VR; Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA; Harvard Medical School, Harvard University, Boston, MA, USA., Ruiz GP; Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA., Nawaz A; Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA; Harvard Medical School, Harvard University, Boston, MA, USA., Brandão BB; Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA; Harvard Medical School, Harvard University, Boston, MA, USA., Dreyfus J; Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA., Pan H; Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA., Kahn CR; Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA; Harvard Medical School, Harvard University, Boston, MA, USA. Electronic address: c.ronald.kahn@joslin.harvard.edu. |
| المصدر: | Cell reports [Cell Rep] 2024 Jul 23; Vol. 43 (7), pp. 114491. Date of Electronic Publication: 2024 Jul 13. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| مواضيع طبية MeSH: | Extracellular Vesicles*/metabolism , Insulin*/metabolism , MicroRNAs*/metabolism , MicroRNAs*/genetics, Animals ; Humans ; Mice ; 3T3-L1 Cells ; Adipocytes/metabolism ; Adipocytes/drug effects ; Gene Expression Regulation ; Hepatocytes/metabolism ; Heterogeneous Nuclear Ribonucleoprotein A1/metabolism ; Heterogeneous Nuclear Ribonucleoprotein A1/genetics ; Insulin Resistance ; Obesity/metabolism ; Obesity/genetics ; Phosphorylation ; Signal Transduction |
| مستخلص: | Tissues release microRNAs (miRNAs) in small extracellular vesicles (sEVs) including exosomes, which can regulate gene expression in distal cells, thus acting as modulators of local and systemic metabolism. Here, we show that insulin regulates miRNA secretion into sEVs from 3T3-L1 adipocytes and that this process is differentially regulated from cellular expression. Thus, of the 53 miRNAs upregulated and 66 miRNAs downregulated by insulin in 3T3-L1 sEVs, only 12 were regulated in parallel in cells. Insulin regulated this process in part by phosphorylating hnRNPA1, causing it to bind to AU-rich motifs in miRNAs, mediating their secretion into sEVs. Importantly, 43% of insulin-regulated sEV-miRNAs are implicated in obesity and insulin resistance. These include let-7 and miR-103, which we show regulate insulin signaling in AML12 hepatocytes. Together, these findings demonstrate an important layer to insulin's regulation of adipose biology and provide a mechanism of tissue crosstalk in obesity and other hyperinsulinemic states. Competing Interests: Declaration of interests The authors declare no competing interests. (Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: CP: Metabolism; CP: Molecular biology; RNA binding proteins; adipocyte; exosomes; extracellular miRNAs; insulin; insulin signaling; miRNA; small extracellular vesicles |
| المشرفين على المادة: | 0 (Heterogeneous Nuclear Ribonucleoprotein A1) 0 (Insulin) 0 (MicroRNAs) |
| تواريخ الأحداث: | Date Created: 20240713 Date Completed: 20240729 Latest Revision: 20240731 |
| رمز التحديث: | 20240801 |
| DOI: | 10.1016/j.celrep.2024.114491 |
| PMID: | 39002127 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2211-1247 |
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| DOI: | 10.1016/j.celrep.2024.114491 |