MicroRNA 33 Regulates the Population of Peripheral Inflammatory Ly6C high Monocytes through Dual Pathways
Open accessAbstract
MicroRNA 33 (miR-33) targets ATP-binding cassette transporter A1 (ABCA1), and its deficiency increases serum high-density lipoprotein (HDL)-cholesterol (HDL-C) and ameliorates atherosclerosis. Although we previously reported that miR-33 deficiency increased peripheral Ly6Chigh monocytes on an ApoE-deficient background, the effect of miR-33 on the monocyte population has not been fully elucidated, especially in a wild-type (WT) background. We found that Ly6Chigh monocytes in miR-33−/− mice were decreased in peripheral blood and increased in bone marrow (BM). Expansion of myeloid progenitors and decreased apoptosis in Lin− Sca1+ c-Kit+ (LSK) cells were observed in miR-33−/− mice. A BM transplantation study and competitive repopulation assay revealed that hematopoietic miR-33 deficiency caused myeloid expansion and increased peripheral Ly6Chigh monocytes and that nonhematopoietic miR-33 deficiency caused reduced peripheral Ly6Chigh monocytes. Expression of high-mobility group AT-hook 2 (HMGA2) targeted by miR-33 increased in miR-33-deficient LSK cells, and its knockdown abolished the reduction of apoptosis. Transduction of human apolipoprotein A1 and ABCA1 in WT mouse liver increased HDL-C and reduced peripheral Ly6Chigh monocytes. These data indicate that miR-33 deficiency affects distribution of inflammatory monocytes through dual pathways. One pathway involves the enhancement of Hmga2 expression in hematopoietic stem cells to increase Ly6Chigh monocytes, and the other involves the elevation of HDL-C to decrease peripheral Ly6Chigh monocytes.
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Inhibition of miR-33a or miR-33a deletion in macrophages affects myeloid cell differentiation, induces M2 macrophage polarization with mitochondrial respiratory and metabolic changes, and enhances autophagy.
“Inhibition of miR-33a or miR-33a deletion in macrophages has been shown to affect myeloid cell differentiation 25) , induce M2 macrophage polarization with mitochondrial respiratory and metabolic changes 26 , 27) , and enhance autophagy 28 , 29) .”
From Critical Role of microRNA-33a/b in Cardiovascular and Metabolic Disease: Molecular Mechanisms and Therapeutic Perspectives (2026) · cites this paper as [25]
The Results section reports that miR-33-deficient mice had increased myeloid progenitors and attributes this to reduced apoptosis in hematopoietic stem cells. This supports the myeloid-cell portion attached to citation 25, but the study does not establish that miR-33a deletion specifically in macrophages causes that change. M2 polarization and autophagy are attached to other citations in the citing sentence. (LLM, conf=0.86)
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Self-citation
- Authors
- Baba, O., Horie, T., Nakao, T., Hakuno, D., Nakashima, Y., Nishi, H., Kuwabara, Y., Nishiga, M., Nishino, T., Ide, Y., Nakazeki, F., Koyama, S., Kimura, M., Hanada, R., Kawahara, M., Kimura, T., & Ono, K.
- Affiliations
- Kyoto University (JP)
- Corresponding author
- Ono, Koh
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2018-07-01
- Volume
- 38
- Issue
- 14
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC6024165
- OpenAlex
- W2799746386
- Cited by
- 12
- References
- 42
- Citations by year
- 2025: 1 · 2022: 3 · 2021: 2 · 2020: 3 · 2019: 3
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular and Cellular Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (17K19590, 17H05599, 17H04177, 16H05297, 17K09860, 15H06335)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- microRNA-33, Ly6Chi monocytes, inflammatory monocytes, HMGA2, ABCA1, apolipoprotein A-I, HDL cholesterol, hematopoietic stem cells, monocyte apoptosis, bone marrow, atherosclerosis
- MeSH terms
- Mice, Knockout, ApoE, Animals, Antigens, Ly, Apolipoproteins E, Hematopoietic Stem Cells, Humans, Cholesterol, HDL, Male, Mice, Inbred C57BL, Monocytes, Recombinant Proteins, Transduction, Genetic, Apolipoprotein A-I, Apoptosis, Mice, Knockout, Myeloid Progenitor Cells, MicroRNAs, Atherosclerosis, Mice, ATP Binding Cassette Transporter 1
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