Department of Endocrinology, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.
Exp Clin Endocrinol Diabetes. 2021 Feb;129(2):131-137. doi: 10.1055/a-1012-8420. Epub 2019 Oct 21.
MicroRNAs serve important roles in the regulation of endoplasmic reticulum stress (ERs). This study aimed to investigate the role of microRNA-320 (miR-320) in the development of ERs and the inflammatory response in 3T3-L1 adipocytes.
The adipose tissue expression levels of miR-320 and ERs markers (GRP78, GRP94, Derlin-1 and CHOP) and the serum concentration of inflammatory cytokines (TNF-α, NF-κB and IL-6) in obese patients were evaluated using quantitative real-time RT-PCR or enzyme-linked immunosorbent assay. The correlation of miR-320 with genes involved in ERs and inflammation was analyzed. The effects of miR-320 on ERs and inflammation were explored using mature 3T3-L1 adipocytes, which were pretreated with palmitic acid (PA).
ERs markers and inflammatory cytokines were all upregulated in obese patients. Adipose tissue miR-320 expression was also increased in obese patients, and had positive correlations with the levels of ERs markers and inflammatory cytokines. After PA treatment, the levels of ERs markers and inflammatory cytokines were elevated significantly in 3T3-L1 adipocytes. Moreover, miR-320 expression was increased in the cells under ERs status. The upregulation of miR-320 could enhance the expression of ERs markers and inflammatory cytokines, but the downregulation of miR-320 resulted in the opposite results.
The data of this study indicate that miR-320 expression is upregulated in ERs status, and the downregulation of miR-320 ameliorates ERs and the inflammatory response in 3T3-L1 adipocytes. We consider that the approaches to decrease miR-320 expression may be novel therapeutic strategies for the treatment of obesity and obesity-related diseases.
微小 RNA(miRNA)在调控内质网应激(ERs)中发挥重要作用。本研究旨在探讨 microRNA-320(miR-320)在 3T3-L1 脂肪细胞 ERs 发育和炎症反应中的作用。
采用实时定量 RT-PCR 或酶联免疫吸附试验评估肥胖患者脂肪组织 miR-320 和 ERs 标志物(GRP78、GRP94、Derlin-1 和 CHOP)的表达水平以及血清中炎症细胞因子(TNF-α、NF-κB 和 IL-6)的浓度。分析 miR-320 与 ERs 和炎症相关基因的相关性。用棕榈酸(PA)预处理成熟的 3T3-L1 脂肪细胞,探讨 miR-320 对 ERs 和炎症的影响。
肥胖患者的 ERs 标志物和炎症细胞因子均上调。肥胖患者脂肪组织 miR-320 的表达也增加,且与 ERs 标志物和炎症细胞因子的水平呈正相关。PA 处理后,3T3-L1 脂肪细胞中 ERs 标志物和炎症细胞因子的水平显著升高。此外,细胞 ERs 状态下 miR-320 的表达增加。miR-320 的上调可增强 ERs 标志物和炎症细胞因子的表达,而 miR-320 的下调则导致相反的结果。
本研究数据表明,miR-320 在 ERs 状态下表达上调,下调 miR-320 可改善 3T3-L1 脂肪细胞的 ERs 和炎症反应。我们认为,降低 miR-320 表达的方法可能是肥胖及其相关疾病治疗的新策略。