Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, China.
Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated To Shandong University, Jinan, 250021, China.
J Endocrinol Invest. 2020 Sep;43(9):1229-1238. doi: 10.1007/s40618-020-01210-y. Epub 2020 Mar 12.
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.
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.
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.
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.
促甲状腺激素（TSH）在脂质代谢调节中起着重要作用。然而，关于 TSH 诱导的非酒精性脂肪性肝病（NAFLD）脂毒性过程中，外泌体所起的作用知之甚少。作为初步步骤，本研究旨在探讨 TSH 刺激 HepG2 细胞衍生的外泌体中蛋白质表达的变化。
用 TSH 处理 HepG2 细胞，收集外泌体，并通过质谱（MS）鉴定蛋白质。进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析，以分析鉴定的蛋白质。
TSH 处理显著增加了 HepG2 细胞中外泌体的产生，并改变了外泌体的蛋白质组谱。在 1728 种蛋白质中，有 140 种鉴定出的蛋白质上调，7 种蛋白质下调。GO 分析和 KEGG 分析表明，这些蛋白质参与了包括代谢、凋亡和炎症在内的多种过程。
我们的初步研究表明，TSH 刺激的肝细胞衍生的外泌体增加，并显示出特定的改变的蛋白质谱，其中许多涉及代谢、信号转导、凋亡和炎症。本研究为 TSH 诱导的 NAFLD 脂毒性的发病机制提供了新的见解。
