在系统性硬化症中,MiR-4769-3p通过负面调节USP18/VDAC2通路来抑制脂肪生成
Bingsi Tang1,2, Jiangfan Yu1,2, Rui Tang3
1Department of Dermatology, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410000, China.
iScience
|August 19, 2024
概括
系统性硬化症 (SSc) 涉及脂肪损失. 微RNA-4769-3p通过准USP18和VDAC2来抑制脂肪细胞的形成,提供了一个潜在的SSc治疗标.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 系统性硬化症 (SSc) 是一种自身免疫性疾病,其特点是涉及多种组织.
- 在SSc中观察到皮下脂肪组织 (SAT) 损失,但其机制尚不清楚.
- 微RNA越来越多地被认为是它们在调节脂肪生成中的作用.
研究的目的:
- 研究微RNAs在SSc.中SAT损失中的作用.
- 确定特定的微RNA及其涉及SSc相关脂肪生成的分子标.
- 探索针对SSc.的微RNA通路的潜在治疗策略.
主要方法:
- 在SSc患者的miR-4769-3p表达的分析和白素诱导的小鼠模型.
- 使用3T3-L1细胞进行体外研究,以评估miR-4769-3p对脂肪生成的影响.
- 路西法酶记者测定证实了miR-4769-3p与USP18.18的结合.
- 西方涂抹和无处不在测试检查蛋白质相互作用和稳定性 (USP18,VDAC2).
主要成果:
- 在SSc患者中,miR-4769-3p被上调,其抑制在小鼠中促进了SAT恢复.
- miR-4769-3p抑制了3T3-L1细胞中的脂肪生成;它的过度表达削弱了脂肪生成.
- miR-4769-3p直接针对USP18,抑制其表达. USP18与VDAC2相互作用,两者在SSc.中都被减少.
- USP18 抑制了 VDAC2 的无处不在和降解. 沉默USP18或VDAC2减弱的脂肪发生.
结论:
- miR-4769-3p通过负调节SSc.中的USP18/VDAC2通路来抑制脂肪生成.
- 该miR-4769-3p/USP18/VDAC2轴代表了一种新的机制,有助于SSc中的SAT损失.
- 准miR-4769-3p或其下游通路可能为SSc.提供治疗途径.
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