通过胰岛素对微RNA表达和分泌到小细胞外囊中的多步调节
Marsel Lino1, Ruben Garcia-Martin1, Vitor Rosetto Muñoz1
1Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, USA; Harvard Medical School, Harvard University, Boston, MA, USA.
Cell reports
|July 13, 2024
概括
胰岛素控制微RNA (miRNA) 从脂肪细胞通过小细胞外囊泡 (sEV) 释放. 这一对新陈代谢至关重要的过程涉及hnnRNPA1蛋白,并影响肥胖和胰岛素抵抗.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 细胞生物学 细胞生物学
- 分子内分泌学分子内分泌学
背景情况:
- 在小细胞外囊泡 (sEV) 中分泌的微RNA (miRNA) 调节远处细胞的基因表达,影响局部和全身新陈代谢.
- 胰岛素是关键的代谢激素,但其对脂肪细胞miRNA分泌的精确调节仍然不清楚.
研究的目的:
- 研究胰岛素如何调节3T3-L1脂肪细胞向sEV分泌miRNA的分泌.
- 阐明胰岛素介导的miRNA分泌背后的分子机制.
- 评估胰岛素调节的sEV-miRNAs在肥胖和胰岛素抵抗方面的相关性.
主要方法:
- 使用了3T3-L1脂肪细胞和AML12肝细胞.
- 在胰岛素刺激下,细胞和sEV中的量化miRNA水平.
- 研究了 hnRNPA1 酸化在通过 AU 丰富动机结合的 miRNA 分泌中的作用.
主要成果:
- 与细胞表达相比,胰岛素不同调节miRNA分泌到sEV中的分泌.
- 胰岛素化 hnRNPA1,促进其与小RNA AU 丰富基因的结合和随后的分泌.
- 相当一部分受胰岛素调节的sEV-miRNA与肥胖和胰岛素抵抗有关,包括let-7和miR-103,它们影响肝脏胰岛素信号传递.
结论:
- 胰岛素信号传递在调节脂肪细胞释放的sEVs的miRNA含量方面发挥着至关重要的作用.
- hnRNPA1在胰岛素诱导的特定miRNAs分泌中起到关键的调解作用.
- 这些发现揭示了在肥胖和高胰岛素状态等代谢疾病中组织交叉通话的新奇机制.
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