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

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

PDF(5097 KB)

Chinese Journal of Clinical Anatomy ›› 2023, Vol. 41 ›› Issue (4) : 440-446. DOI: 10.13418/j.issn.1001-165x.2023.4.12

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

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

Author information +

History +

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

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

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

References

[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.