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

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

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

  1. 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

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

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