Center for Biomedical Research of La Rioja (CIBIR), Neurodegeneration Area, Biomarkers and Molecular Signaling Group, Piqueras 98, 26006 Logroño, Spain.
Cells. 2020 May 11;9(5):1187. doi: 10.3390/cells9051187.
In addition to its predominant role in lipid metabolism and body weight control, has emerged recently as a potential new target for the treatment of various diseases. Sterculic acid (SA) is a cyclopropene fatty acid with numerous biological activities, generally attributed to its Stearoyl-CoA desaturase (SCD) inhibitory properties. Additional effects exerted by SA, independently of SCD inhibition, may be mediating anti-inflammatory and protective roles in retinal diseases such as age-related macular degeneration (AMD), but the mechanisms involved are poorly understood. In order to provide insights into those mechanisms, genome-wide transcriptomic analyses were carried out in mRPE cells exposed to SA for 24 h. Integrative functional enrichment analysis of genome-wide expression data provided biological insight about the protective mechanisms induced by SA. On the one hand, pivotal genes related to fatty acid biosynthesis, steroid biosynthesis, cell death, actin-cytoskeleton reorganization and extracellular matrix-receptor interaction were significantly downregulated by exposition to SA. On the other hand, genes related to fatty acid degradation and beta-oxidation were significantly upregulated. In conclusion, SA administration to RPE cells regulates crucial pathways related to cell proliferation, inflammation and cell death that may be of interest for the treatment of ocular diseases.
除了在脂质代谢和体重控制中起主要作用外，最近还发现它可能成为治疗各种疾病的新靶点。甾醇酸（SA）是一种具有多种生物活性的环丙烯脂肪酸，通常归因于其硬脂酰辅酶 A 去饱和酶（SCD）抑制特性。SA 发挥的其他作用（独立于 SCD 抑制）可能在年龄相关性黄斑变性（AMD）等视网膜疾病中发挥抗炎和保护作用，但相关机制尚不清楚。为了深入了解这些机制，我们对暴露于 SA 24 小时的 mRPE 细胞进行了全基因组转录组分析。全基因组表达数据的综合功能富集分析提供了关于 SA 诱导的保护机制的生物学见解。一方面，与脂肪酸生物合成、类固醇生物合成、细胞死亡、肌动蛋白细胞骨架重排和细胞外基质-受体相互作用相关的关键基因被 SA 暴露显著下调。另一方面，与脂肪酸降解和β-氧化相关的基因显著上调。总之，SA 给药至 RPE 细胞调节与细胞增殖、炎症和细胞死亡相关的关键途径，这可能对眼部疾病的治疗有意义。
