miR-33 和 miR-34a 在衰老眼中对 ABCA1 的调控
Regulation of ABCA1 by miR-33 and miR-34a in the Aging Eye.
机构信息
Laboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Schlieren, Switzerland.
出版信息
Adv Exp Med Biol. 2023;1415:55-59. doi: 10.1007/978-3-031-27681-1_9.
Many age-related diseases, including age-related macular degeneration (AMD), go along with local lipid accumulation and dysregulated lipid metabolism. Several genes involved in lipid metabolism, including ATP-binding cassette transporter A1 (ABCA1), were associated with AMD through genome-wide association studies. Recent studies have shown that loss of ABCA1 in the retinal pigment epithelium (RPE) leads to lipid accumulation and RPE atrophy, a hallmark of AMD, and that antagonizing ABCA1-targeting microRNAs (miRNAs) attenuated pathological changes to the RPE or to macrophages. Here, we focus on two lipid metabolism-modulating miRNAs, miR-33 and miR-34a, which show increased expression in aging RPE cells, and on their potential to regulate ABCA1 levels, cholesterol efflux, and lipid accumulation in AMD pathogenesis.
许多与年龄相关的疾病，包括年龄相关性黄斑变性（AMD），都伴随着局部脂质积累和脂质代谢失调。通过全基因组关联研究发现，几种参与脂质代谢的基因，包括三磷酸腺苷结合盒转运体 A1（ABCA1），与 AMD 有关。最近的研究表明，视网膜色素上皮（RPE）中 ABCA1 的缺失导致脂质积累和 RPE 萎缩，这是 AMD 的一个标志，而拮抗 ABCA1 靶向 microRNAs（miRNAs）则可以减轻 RPE 或巨噬细胞的病理变化。在这里，我们重点关注两种脂质代谢调节 miRNA，miR-33 和 miR-34a，它们在衰老的 RPE 细胞中表达增加，并探讨它们在调节 ABCA1 水平、胆固醇外排和 AMD 发病机制中的脂质积累中的潜在作用。
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