Downregulation of miR-320 Alleviates Endoplasmic Reticulum Stress and Inflammatory Response in 3T3-L1 Adipocytes
Downregulation of miR-320 Alleviates Endoplasmic Reticulum Stress and Inflammatory Response in 3T3-L1 Adipocytes
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DOI：
10.1055/a-1012-8420
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发表时间：
2021-02-01
影响因子：
1.8
通讯作者：
Li, Xiaohua
中科院分区：
文献类型：
--
作者：
Liu, Lu;Li, Xiaohua
目的microRNAs在内质网应激(ERs)的调节中发挥重要作用。本研究旨在探讨microRNA-320(miR-320)在3T3-L1脂肪细胞内质网形成和炎症反应中的作用。材料与方法采用实时定量RT-PCR和酶联免疫吸附试验检测肥胖患者脂肪组织中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-kappa B和IL-6)的浓度。分析miR-320与ER和炎症相关基因的相关性。用棕榈酸(PA)处理3T3-L1成熟脂肪细胞，观察miR-320对ER和炎症反应的影响。结果肥胖患者ER标志物和炎症细胞因子均上调。肥胖患者脂肪组织miR-320表达增加，并与ER标志物和炎性细胞因子水平呈正相关。PA处理后，3T3-L1脂肪细胞ERs标志物和炎性细胞因子水平显著升高。此外，在ERS状态下，miR-320的表达增加。MiR-320上调可促进ERs标志物和炎性细胞因子的表达，而miR-320下调则相反。结论本研究结果表明，在内质网状态下miR-320表达上调，miR-320下调可改善3T3-L1脂肪细胞的ER和炎症反应。我们认为，降低miR-320表达的方法可能是治疗肥胖和肥胖相关疾病的新的治疗策略。
Objective 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.Materials and Methods 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-alpha, NF-kappa B 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).Results 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.Conclusion 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.