microRNA-125a靶向sortilin抑制巨噬细胞脂质蓄积与主动脉粥样硬化病变机制研究

doi:10.13418/j.issn.1001-165x.2023.4.12

中国临床解剖学杂志 ›› 2023, Vol. 41 ›› Issue (4): 440-446.doi: 10.13418/j.issn.1001-165x.2023.4.12

microRNA-125a靶向sortilin抑制巨噬细胞脂质蓄积与主动脉粥样硬化病变机制研究

吕运成¹，明新月¹，刘芳¹，陈诗芮¹，彭田红²，欧阳曙晖³*

1.桂林医学院广西糖尿病重点实验室，广西桂林 541199； 2.南华大学衡阳医学院应用解剖与生殖研究所，湖南衡阳 421001； 3.南华大学衡阳医学院附属第一医院内分泌与代谢疾病研究所，湖南衡阳 421001

收稿日期:2022-08-11 出版日期:2023-07-25 发布日期:2023-08-02
通讯作者: 欧阳曙晖，实习研究员，E-mail：1299315234@qq.com
作者简介:吕运成（1979-），博士，研究方向为脂代谢紊乱相关疾病，E-mail：anthony0723@163.com
基金资助:
广西自治区自然科学基金（2019JJA140728）；湖南省自然科学基金项目（2020JJ4532）

MicroRNA-125a-targeted sortilin suppresses macrophage lipid accumulation and aortic atherogenesis

Lv Yuncheng¹, Ming Xinyue¹, Liu Fang¹, Chen Shirui¹, Peng Tianhong², Ouyang Shuhui³*

1. Guangxi Key Laboratory of Diabetic System Medicine, Guilin Medical University, Guilin 541199, Guangxi Province, China; 2.Clinical Anatomy & Reproductive Medicine Application Institute, Hengyang Medical College, University of South China, Hengyang 421001, Hunan Province, China; 3. Department of Endocrinology and Metabolic Diseases, the First Affiliated Hospital, Hengyang Medical College, University of South China, Hengyang 421001, Hunan Province, China

Received:2022-08-11 Online:2023-07-25 Published:2023-08-02

摘要/Abstract

摘要： 目的探讨miR-125a对巨噬细胞脂质代谢及主动脉粥样硬化（atherosclerosis，AS）病变的影响及作用机制。方法油红O及比色法检测巨噬细胞内脂滴情况及脂质含量；生物信息学预测miR-125a下游靶标；双荧光素酶报告基因验证miR-125a与sortilin mRNA靶向结合；qPCR、Western blot和免疫组化检测荷脂THP-1巨噬细胞和低密度脂蛋白受体敲除（LDLR?/?）小鼠中miR-125a及sortilin表达；全自动生化分析仪测定血脂改变；组织染色显示主动脉AS斑块面积及脂质沉积情况。结果过表达miR-125a可减轻THP-1巨噬细胞内脂质蓄积；生信分析和荧光素酶报告基因显示sortilin mRNA是miR-125a的作用靶标；过表达miR-125a可下调巨噬细胞sortilin表达，减少胞内脂滴数量及脂质含量，改善LDLR?/?小鼠血脂谱，抑制主动脉脂质沉积及AS病变面积。结论 miR-125a可通过下调sortilin表达抑制巨噬细胞脂质蓄积及主动脉AS病变。

关键词: miR-125a； , , sortilin； , , 巨噬细胞； , , 脂质蓄积； , , 动脉粥样硬化

Abstract: Objective To investigate the effect and mechanism of miR-125a on the lipid metabolism of macrophages and the development of aortic atherosclerosis (AS) in LDLR?/? mice. Methods The lipid accumulation in macrophages was evaluated by Oil red O staining and colorimetry. The bioinformatics was used to predict the target gene of miR-125a. Double luciferase reporter gene analyzed the targeted binding between miR-125a and SORT1. The expressions of miR-125a and sortilin were detected in lipid-laden THP-1 macrophages and low-density lipoprotein receptor knockout (LDLR?/?) mice by qPCR、Western blot and immunohistochemistry. The blood lipid level was measured with automatic biochemical analyzer. The aortic AS plaque and lipid accumulation were showed by histological staining. Results Overexpression of miR-125a reduced lipid accumulation in THP-1 macrophages. Bioinformatics analysis and luciferase reporter gene showed that sortilin mRNA was a potential target of miR-125a. Overexpression of miR-125a suppressed sortilin expression and lipid accumulation in macrophages. miR-125a also ameliorated the blood lipid profile and reduced the plaque area of aortic AS in LDLR?/? mice. Conclusions miR-125a inhibits macrophage lipid accumulation and the progression of aortic AS by down-regulating sortilin expression.

Key words: miR-125a; , , sortilin; , , Macrophages; , , Lipid accumulation; , , Atherosclerosis

中图分类号:

吕运成, 明新月, 刘芳, 陈诗芮, 彭田红, 欧阳曙晖. microRNA-125a靶向sortilin抑制巨噬细胞脂质蓄积与主动脉粥样硬化病变机制研究[J]. 中国临床解剖学杂志, 2023, 41(4): 440-446.

Lv Yuncheng, Ming Xinyue, Liu Fang, Chen Shirui, Peng Tianhong, Ouyang Shuhui. MicroRNA-125a-targeted sortilin suppresses macrophage lipid accumulation and aortic atherogenesis[J]. Chinese Journal of Clinical Anatomy, 2023, 41(4): 440-446.

参考文献 11

[1]	姜志胜, 唐朝克, 秦树存, 等. 动脉粥样硬化学[M]. 北京: 北京科学出版社, 2017: 29-56, 67-140.
[2]	王声全, 张光琼, 沈祥春, 等. 艳山姜挥发油调控PPARγ/ABCA1信号抑制巨噬细胞源性泡沫细胞形成的作用机制[J]. 中华中医药杂志, 2022, 37(2): 1118-1122.
[3]	Li H, Yu XH, Tang CK, et al. Hepatic cholesterol transport and its role in non-alcoholic fatty liver disease and atherosclerosis[J]. Prog Lipid Res, 2021, 83: 101109. DOI: 10.1016/j.plipres.2021.101109.
[4]	Ouyang SH, Jia B, Lv YC, et al. Mechanism underlying the regulation of sortilin expression and its trafficking function[J]. J Cell Physiol, 2020, 235(12): 8958-8971. DOI: 10.1002/jcp.29818.
[5]	Lv YC, Yang J, Zhong LY, et al. Sortilin promotes macrophage cholesterol accumulation and aortic atherosclerosis through lysosomal degradation of ATP-binding cassette transporter A1 protein[J]. ABBS, 2019, 51(5): 471-483. DOI: 10.1093/abbs/gmz029.
[6]	Clark JR, Gemin M, Koschinsky ML, et al. Sortilin enhances secretion of apolipoprotein(a) through effects on apolipoprotein B secretion and promotes uptake of lipoprotein(a)[J]. J Lipid Res, 2022, 63(6): 100216. DOI: 10.1016/j.jlr.2022.100216.
[7]	Şimsek Z, Alizade E, Pala S, et al. Serum sortilin as a predictor of stroke in patients with intermediate carotid artery stenosis[J]. Vascular, 2022, 31(2): 317-324. DOI: 10.1177/17085381211067051.
[8]	Li H, Wang XG, Luo B, et al. The up-regulation of endothelin-1 and down-regulation ofmiR-125a-5p, -155, and -199a/b-3p in human atherosclerotic coronary artery[J]. Cardiovasc Pathol, 2014, 23(4): 217-223. DOI: 10.1016/j.carpath.2014.03.009.
[9]	Chen K, He HH, Mo ZH, et al. miR-125a-3p and miR-483-5p promote adipogenesis via suppressing the RhoA/ROCK1/ERK1/2 pathway in multiple symmetric lipomatosis[J]. Sci Rep, 2015, 5: 1-15. DOI: 10.1038/srep11909.
[10]	Chen T, Huang ZQ, Wang CQ, et al. MicroRNA-125a-5p partly regulates the inflammatory response, lipid uptake, and ORP9 expression in oxLDL-stimulated monocyte/macrophages[J]. Cardiovasc Res, 2009, 83(1): 131-139. DOI: 10.1093/cvr/cvp121.
[11]	Hwang SJ, Ahn BJ, Lee HJ, et al. miR-125a-5p attenuates macrophage-mediated vascular dysfunction by targeting Ninjurin1[J]. Cell Death Differ, 2022, 29(6): 1199-1210. DOI: 10.1038/s41418-021-00911-y.

[1]	江剑宏, 段仁鹏, 李晓锋. 国人胆道三维重建解剖变异应用研究[J]. 中国临床解剖学杂志, 2024, 42(1): 1-4.
[2]	郭红志, 王瑜, 张加琪, 梁海彬, 马梓玮, 冯伟, 吴忧, 司子燚. 血管铸型结合CT三维模型评估先兆子痫胎盘血管结构[J]. 中国临床解剖学杂志, 2024, 42(1): 5-10.
[3]	李佳伟, 张静, 李灿然, 兰文杰, 籍庆余, 郭志勇, 张云凤, 刘启, 陈清威, 李筱贺. 蒙古族人群股骨近端解剖参数X线测量[J]. 中国临床解剖学杂志, 2024, 42(1): 11-16.
[4]	李琨, 张燕, 郭冉, 郝咪咪, 吴轩宇, 徐艺芳, 王超群, 马文童, 张灵淇, 杨宏宇, 李志军, 张少杰, 王星. 儿童及青少年枕颈角与后枕颈角数字化测量及其临床意义[J]. 中国临床解剖学杂志, 2024, 42(1): 17-20.
[5]	李文, 杨思艺, 黄蕾, 卿霁雯, 蒋松涛, 张磊. 基于MRI探讨Lisfranc韧带的形态学特点及临床意义[J]. 中国临床解剖学杂志, 2024, 42(1): 21-25.
[6]	李凡凡, 徐阳, 王晓旭. 紫草素调节Nrf2/HO-1信号通路对实验性大鼠肉芽肿性小叶性乳腺炎的治疗作用研究[J]. 中国临床解剖学杂志, 2024, 42(1): 26-32.
[7]	王兴航, 丁佳媛, 李放, 包翠芬, 阎丽菁. 人参皂苷Rg1通过抑制NLRP3炎症小体途径减轻氧糖剥夺/复供后小胶质细胞炎症反应[J]. 中国临床解剖学杂志, 2024, 42(1): 33-41.
[8]	程莹莹, 武建军, 蔡海燕, 焦旭文, 马江波, 丁银秀. 体外炎性诱导星形胶质细胞激活及功能分析[J]. 中国临床解剖学杂志, 2024, 42(1): 42-46.
[9]	祁志, 杨力, 贾秋叶, 陈浩伦, 段兆达, 吴春云. 依达拉奉经MAPKs通路对脂多糖激活的小胶质细胞Sirt3表达调控[J]. 中国临床解剖学杂志, 2024, 42(1): 47-53.
[10]	张晶晶, 王洪新. 黄芩苷通过PDGF/P38 MAPK信号通路对肺动脉高压大鼠的保护作用[J]. 中国临床解剖学杂志, 2024, 42(1): 54-58.
[11]	乐钦, 陈荣丽, 熊婧熙, 王婷怡, 蔡志恒, 易秋实, 曾心怡. 白芨多糖对大鼠跨区皮瓣choke区的影响[J]. 中国临床解剖学杂志, 2024, 42(1): 59-64.
[12]	李笑予, 张磊, 付磊, 李东波, 汪国友. 三步接骨法治疗Sanders Ⅱ型跟骨骨折的有限元研究[J]. 中国临床解剖学杂志, 2024, 42(1): 65-70.
[13]	吴研飞, 马剑雄, 卢斌, 王颖, 柏豪豪, 靳洪震, 马信龙. CT后处理技术重建CT值与终板抗压强度的相关性研究[J]. 中国临床解剖学杂志, 2024, 42(1): 71-76.
[14]	庄万强, 唐毅, 骆勇刚, 张辉. 关节镜联合胫骨高位截骨术对髌骨位置及髌股关节功能影响的早中期回顾性研究[J]. 中国临床解剖学杂志, 2024, 42(1): 77-82.
[15]	罗鹰, 窦伟誉, 吴小杭, 陈璟昆, 彭昌贵, 潘剑英 . 微创海马钢板内固定治疗跟骨骨折并发症的影响因素[J]. 中国临床解剖学杂志, 2024, 42(1): 83-88.

microRNA-125a靶向sortilin抑制巨噬细胞脂质蓄积与主动脉粥样硬化病变机制研究

MicroRNA-125a-targeted sortilin suppresses macrophage lipid accumulation and aortic atherogenesis

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献 11

相关文章 15

Metrics

本文评价

推荐阅读 0