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A&R: 雌激素诱导的hsa-miR-10b-5p在系统性红斑狼疮患者的T细胞中升高,并下调富含丝氨酸/精氨酸的剪接因子1

2021-12-07 MedSci原创 MedSci原创

本研究旨在研究雌激素的作用和SRSF1的转录后调控机制在T细胞和SLE中的作用。

     背景/目的:自身免疫性疾病对女性的影响比对男性的影响更大。雌激素与免疫细胞功能障碍有关,但其精确的分子作用尚不完全清楚。该研究团队最近确定了富含丝氨酸/精氨酸的剪接因子1 (SRSF1)T细胞功能和自身免疫中的新作用。系统性红斑狼疮(SLE)患者的T 细胞SRSF1水平降低,并且与活动性疾病和合并症有关。然而,控制SRSF1表达的分子机制尚不清楚。Srsf1信使RNA (mRNA)有一个长的3'-非编码区(3'-UTR),表明转录后调控的可能性。本研究旨在研究雌激素的作用和SRSF1的转录后调控机制在T细胞和SLE中的作用。

      方法Srsf1-3'-UTR生物信息学分析提示多个microRNAmiRNAmiR)结合位点。额外的筛选和文献搜索缩小到hsa-miR-10b-5p做进一步研究。通过定量逆转录聚合酶链反应(qRT-PCR)评估健康个体和SLE患者的外周血T细胞的mRNAmiRNA表达,并通过免疫印迹评估SRSF1蛋白水平。T细胞用β-雌二醇培养,瞬时转染用于过表达miRNA。荧光素酶测定用于测量 3'-UTR 活性。

     结果研究证明雌激素增加了人T细胞中hsa-miR-10b-5p的表达,并且hsa-miR-10b-5p下调了SRSF1蛋白的表达。从机制上讲,hsa-mir-10b-5p通过控制SRSF13'-UTR活性在转录后调节SRSF1重要的是,与健康男性相比,健康女性T细胞中的hsa-miR-10b-5p表达水平升高,SLE患者T细胞中的hsa-miR-10b-5p表达水平也升高。

     结论:该研究在免疫细胞中发现了雌激素和基因调控之间以前未被认识的分子联系,可能与全身性自身免疫疾病相关。

 

出处:

Ramanujan, S.A., Cravens, E.N., Krishfield, S.M., Kyttaris, V.C. and Moulton, V.R. (2021), Estrogen-Induced hsa-miR-10b-5p Is Elevated in T Cells From Patients With Systemic Lupus Erythematosus and Down-Regulates Serine/Arginine-Rich Splicing Factor 1. Arthritis Rheumatol, 73: 2052-2058. https://doi.org/10.1002/art.41787

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    2022-09-01 smallant2002
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    2021-12-09 zhouqu_8
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    2021-12-07 ms4000002104268667

    谢谢

    0

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