Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration
Open accessAbstract
Macrophage aging is pathogenic in diseases of the elderly, including age-related macular degeneration (AMD), a leading cause of blindness in older adults. However, the role of microRNAs, which modulate immune processes, in regulating macrophage dysfunction and thereby promoting age-associated diseases is underexplored. Here, we report that microRNA-150 (miR-150) coordinates transcriptomic changes in aged murine macrophages, especially those associated with aberrant lipid trafficking and metabolism in AMD pathogenesis. Molecular profiling confirmed that aged murine macrophages exhibit dysregulated ceramide and phospholipid profiles compared with young macrophages. Of translational relevance, upregulation of miR-150 in human peripheral blood mononuclear cells was also significantly associated with increased odds of AMD, even after controlling for age. Mechanistically, miR-150 directly targets stearoyl-CoA desaturase-2, which coordinates macrophage-mediated inflammation and pathologic angiogenesis, as seen in AMD, in a VEGF-independent manner. Together, our results implicate miR-150 as pathogenic in AMD and provide potentially novel molecular insights into diseases of aging.
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Cytokines activate downstream signaling pathways of pattern recognition receptors, causing systemic chronic inflammatory responses in the body.
“Cytokines activate downstream signaling pathways of pattern recognition receptors,203 causing systemic chronic inflammatory responses in the body.204”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [204]
The Introduction (page unavailable) says aged macrophages have a proangiogenic cytokine-expression profile that leads to dysregulated inflammation. It does not say that cytokines activate downstream pattern-recognition-receptor pathways or cause systemic chronic inflammation; its discussion is limited to aged macrophages. (LLM, conf=0.78)
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- Authors
- Lin, J. B., Moolani, H. V., Sene, A., Sidhu, R., Kell, P., Lin, J. B., Dong, Z., Ban, N., Ory, D. S., & Apte, R. S.
- Affiliations
- Department of Ophthalmology and Visual Sciences,
- Diabetic Cardiovascular Disease Center,
- Washington University in St. Louis (US)
- Corresponding author
- Apte, Rajendra S.
- ORCID
- Venue
- JCI Insight
- Published
- 2018-04-05
- Volume
- 3
- Issue
- 7
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC5928865
- OpenAlex
- W2796340801
- Cited by
- 54
- References
- 57
- Citations by year
- 2026: 5 · 2025: 1 · 2024: 13 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 5 · 2018: 5
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- JCI Insight (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by)
- Funders
- Glenn Foundation for Medical Research
- Research to Prevent Blindness
- Washington University in St. Louis
- Institute of Clinical and Translational Sciences
- VitreoRetinal Surgery Foundation
- National Institutes of Health (UL1TR000448, UL1TR002345)
- National Eye Institute (R01EY019287, P30EY002687)
- National Institute of General Medical Sciences (T32GM007200)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK020579)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
- Keywords
- miR-150, age-related macular degeneration, pathological angiogenesis, lipid metabolism, ceramide, phospholipids, macrophage inflammation, peripheral blood mononuclear cells, VEGF-independent angiogenesis, age-related diseases
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Aging, Animals, Ceramides, Female, Humans, Macrophages, Macular Degeneration, Male, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged, Neovascularization, Pathologic, Phospholipids, Stearoyl-CoA Desaturase, Sequence Analysis, RNA, Gene Expression Profiling, MicroRNAs, Lipid Metabolism, Mice, Primary Cell Culture
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