Journal of Endocrinological Investigation ( IF 3.9 ) Pub Date : 2020-03-12 , DOI: 10.1007/s40618-020-01210-y S Ma 1, 2 , S Shao 1, 2 , C Yang 2 , Z Yao 2 , L Gao 3, 4 , W Chen 3, 4
Background
Thyroid-stimulating hormone (TSH) plays an important role in the regulation of lipid metabolism. However, little is known about the role that exosomes play in the process of TSH-induced lipotoxicity in non-alcoholic fatty liver disease (NAFLD). As a preliminary step, the present study set out to investigate alterations in protein expression in exosomes derived from TSH-stimulated HepG2 cells.
Methods
HepG2 cells were treated with TSH, exosomes were collected, and proteins were identified by mass spectrometry (MS). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis were performed to analyze the identified proteins.
Results
TSH treatment significantly increased exosomal production and changed the exosomal proteomic profile in HepG2 cells. Among the 1728 proteins, 140 identified proteins were upregulated and seven proteins were downregulated. GO analysis and KEGG analysis revealed that these proteins were involved in multiple processes including metabolism, apoptosis, and inflammation.
Conclusion
Our preliminary study demonstrated that exosomes derived from TSH-stimulated hepatocytes were increased and showed a specific altered spectrum of proteins, many of which were involved in metabolism, signal transduction, apoptosis, and inflammation. This study offers new insights into the pathogenesis of TSH-induced lipotoxicity in NAFLD.
中文翻译:
初步研究:由甲状腺刺激激素刺激的HepG2细胞衍生的外泌体的蛋白质组学分析。
背景
促甲状腺激素(TSH)在调节脂质代谢中起重要作用。但是,关于外来体在非酒精性脂肪肝疾病(NAFLD)中TSH诱导的脂毒性过程中所起的作用知之甚少。作为第一步,本研究着手研究由TSH刺激的HepG2细胞衍生的外泌体中蛋白质表达的变化。
方法
用TSH处理HepG2细胞,收集外泌体,并通过质谱(MS)鉴定蛋白质。进行了基因本体论(GO)和《京都议定书》基因与基因组百科全书(KEGG)途径分析,以分析鉴定出的蛋白质。
结果
TSH处理显着增加了HepG2细胞的外泌体生产并改变了外泌体蛋白质组学特征。在1728种蛋白质中,有140种已鉴定的蛋白质被上调,而七个蛋白质被下调。GO分析和KEGG分析表明,这些蛋白质参与了多个过程,包括代谢,细胞凋亡和炎症。
结论
我们的初步研究表明,TSH刺激的肝细胞衍生的外泌体增加,并显示出特定的蛋白质光谱变化,其中许多与代谢,信号转导,细胞凋亡和炎症有关。这项研究为TSH诱导的NAFLD脂毒性的发病机理提供了新的见解。