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Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration
Jonathan B. Lin, … , Daniel S. Ory, Rajendra S. Apte
Jonathan B. Lin, … , Daniel S. Ory, Rajendra S. Apte
Published April 5, 2018
Citation Information: JCI Insight. 2018;3(7):e120157. https://doi.org/10.1172/jci.insight.120157.
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Research Article Aging Ophthalmology

Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration

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Abstract

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.

Authors

Jonathan B. Lin, Harsh V. Moolani, Abdoulaye Sene, Rohini Sidhu, Pamela Kell, Joseph B. Lin, Zhenyu Dong, Norimitsu Ban, Daniel S. Ory, Rajendra S. Apte

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Figure 1

microRNA-150 is upregulated in aged macrophages of diverse origins.

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microRNA-150 is upregulated in aged macrophages of diverse origins.
(A) ...
(A) In young macrophages, 10 microRNAs were downregulated similarly in response to acetylated low-density lipoprotein (acLDL) and oxidized low-density lipoprotein (oxLDL). (B) In aged macrophages, 5 microRNAs were dysregulated similarly in response to acLDL and oxLDL. (C) In untreated (UT), acLDL-treated, and oxLDL-treated macrophages, 5 microRNAs were dysregulated similarly in aged and young macrophages under the same treatment conditions. microRNA-150 was upregulated in aged peritoneal macrophages (PM) (D; n = 12/group; 2-tailed Mann-Whitney U test), aged splenic macrophages (SM) (E; n = 13/group; 2-tailed Mann-Whitney U test), and aged BM-derived macrophages (BMDM) (F; n = 10/group; 2-tailed, unpaired Welch’s t test). (G) Upregulation of microRNA-150 in aged PMs was not affected by treatment with acLDL (n = 7/group; 2-tailed Mann-Whitney U test), oxLDL (n = 7/group; 2-tailed, unpaired Welch’s t test), or LPS (n = 5/group; 2-tailed Mann-Whitney U test). (H) Upregulation of microRNA-150 in aged BMDMs was not affected by treatment with oxLDL (n = 5/group; 2-tailed Mann-Whitney U test) or LPS (n = 5/group; 2-tailed Mann-Whitney U test). Open circles depict individual data points; graphs depict mean ± SEM (A–F) (*P < 0.05; **P < 0.01; ****P < 0.0001).

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