miR-378a Modulates Macrophage Phagocytosis and Differentiation through Targeting CD47-SIRPα Axis in Atherosclerosis
Open accessAbstract
Background: Signal regulatory protein alpha (SIRPa) is an essential signalling molecule that modulates inflammatory responses in macrophages. However, the regulation of SIRPs and its dynamic changes in macrophages under inflammatory stimulation in atherosclerosis remain uncertain. Objective: The study aimed to identify the miRNAs that regulate SIRPa transcription and their roles in modulating phagocytosis, differentiation and cholesterol efflux in macrophages. Methods: ApoE knockout mice were fed with a high‐fat diet for 12 weeks. Intimal lesion areas and lipid accumulation were assessed by haematoxylin and eosin (HE) and oil red O staining. The expression of mRNAs/miRNAs was assessed by RNA‐seq (RNA sequencing) and RT‐qPCR (real‐time quantitative polymerase chain reaction). The identification of miR‐378a associated with SIRPa regulation in macrophages induced by ox‐LDL was confirmed by RT‐qPCR and Western blot. The phagocytosis and differentiation of macrophages were detected to figure out the role of miR‐378a and SIRPa. Results: SIRPa was proved to be a target of miR‐378a. Reduced miR‐378a can promote the expression of SIRPa. RNA‐seq data showed that the levels of mRNA associated with macrophage phenotypes and SIRPa‐CD47 axis were increasing significantly with a decreasing phagocytic phenotype in ApoE −/− mice vs wild‐type (WT) mice ( P < 0.01). The level of miR‐378a was reduced in the aorta of ApoE −/− mice vs WT mice. The experiment in vitro showed that overexpression of miR‐378a in macrophages decreased the level of Sirpa mRNA obviously vs control ( P < 0.01). The phagocytic activity of miR‐378a–transfected macrophages was promoted vs control ( P < 0.05). miR‐378a significantly depleted Sirpa levels in oxidized low‐density lipoprotein (ox‐LDL)‐stimulated macrophages ( P < 0.05), and depletion of miR‐378a reversed Sirpa reduction obviously ( P < 0.05). miR‐378a promoted the secretion of TNF‐a and IL‐6 indirectly. Conclusion: It has been demonstrated that miR‐378a regulates SIRPa‐mediated phagocytosis and polarization of macrophages by a direct or indirect way. This research may provide a new path to promote reverse cholesterol transport of macrophages and hinder the progress of atherosclerosis.
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CD47-SIRPα pathway activation correlates with the expression level of miR-378a; miR-378a affects phagocytosis and macrophage differentiation by targeting CD47-SIRPα.
“On the other hand, Chen et al. correlated CD47-SIRPα pathway activation with the expression level of miR-378a. The authors indicated that miR-378a affects phagocytosis and macrophage differentiation by targeting CD47-SIRPα [175].”
From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [175]
The Discussion states that miR-378a modulates macrophage phagocytosis and differentiation through the CD47–SIRPα axis. Sections 2.6 and 2.8 show that changing miR-378a levels changes SIRPα expression, but they do not establish a correlation with pathway activation specifically. (LLM, conf=0.82)
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MicroRNAs as Regulators of Phagocytosis
Gierlikowski, W., & Gierlikowska, B. (2022) · Cells · doi:10.3390/cells11091380 · Cited by 25 · see citing works
- Authors
- Chen, W., Li, X., Wang, J., Song, N., Zhu, A., & Jia, L.
- Affiliations
- Liaoning University of Traditional Chinese Medicine (CN)
- Guangzhou University of Chinese Medicine (CN)
- Zhejiang Chinese Medical University (CN)
- Corresponding author
- Chen, Wenna
- Venue
- Scandinavian Journal of Immunology
- Publisher
- Wiley
- Published
- 2019-04-22
- Volume
- 90
- Issue
- 1
- Pages
- e12766-e12766
- ISSN
- 0300-9475 (ISSN-L)
- 1365-3083
- OpenAlex
- W2930866301
- Cited by
- 36
- References
- 2
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 8 · 2021: 8 · 2020: 6 · 2019: 3
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Scandinavian Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (No. 81300229 and 81874372)
- Liaoning University of Traditional Chinese Medicine (ZYZX1602)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- miR-378a, SIRPα, CD47-SIRPα axis, macrophage phagocytosis, macrophage differentiation, atherosclerosis, oxidized LDL, cholesterol efflux, TNF-α, ApoE-deficient mice, high-fat diet, microRNA target regulation, macrophage polarization, lipid accumulation
- MeSH terms
- Mice, Knockout, ApoE, Animals, Cell Differentiation, Cells, Cultured, Cholesterol, Humans, Inflammation, Macrophages, Phagocytosis, Receptors, Immunologic, Signal Transduction, MicroRNAs, Atherosclerosis, Mice, CD47 Antigen, Diet, High-Fat
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