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

ABSTRACT: Macrophage aging is pathogenic in numerous age-associated diseases, including age-related macular degeneration. The purpose of this experiment was to profile microRNA expression in young and aged macrophages at baseline and in response to oxLDL and acLDL.

ORGANISM(S): Mus musculus synthetic construct

PROVIDER: GSE111304 | GEO | 2018/04/05

REPOSITORIES: GEO

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

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

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

Project description: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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Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration: part I

Project description:Macrophage microRNA-150 promotes pathological angiogenesis as seen in age-related macular degeneration: part I

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

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

Project description:We identified that microRNA-150 is upregulated in aged macrophages of diverse origins and therefore may mechanistically skew them towards a disease-promoting phenotype. The purpose of this experiment was to identify how the murine transcriptome changes with microRNA-150 overexpression.

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