Zhang Liya, Wu Kunpeng, Bo Tao, Zhou Lingyan, Gao Ling, Zhou Xiaoming, Chen Wenbin
Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong 250021, P.R. China.
Exp Ther Med. 2020 Feb;19(2):897-906. doi: 10.3892/etm.2019.8281. Epub 2019 Dec 4.
Subclinical hypothyroidism (SCH) is becoming a global health problem due to its increasing prevalence and potential adverse effects, including cardiovascular diseases and nonalcoholic fatty liver disease (NAFLD). However, the association between SCH and NAFLD remains controversial. MicroRNAs (miRNAs/miRs) have been reported to be implicated in lipid metabolism disorders; however, how miRNAs regulate hepatic lipid metabolism in SCH mice remains unknown. The present study investigated miRNA alterations and proteome profiles in an SCH mouse model, which was generated by methimazole administration in mice for 16 weeks. Next, the profiles of 17 miRNAs that are critical to hepatic lipid metabolism and the proteome were investigated using reverse transcription-quantitative polymerase chain reaction and iTRAQ labeling in the liver specimens of SCH (n=9) and control (n=7) mice. Putative target prediction of miRNAs was also conducted using TargetScan and miRanda. Compared with the control mice, SCH mice had 8 miRNAs and 36 proteins with significantly different expression in the liver tissues. Furthermore, a regulatory module containing 3 miRNAs (miR-34a-5p, miR-24-3p and miR-130a-3p) and 4 proteins (thioredoxin, selenium-binding protein 2, elongation factor 1β and prosaposin) was identified. Overall, integrated analysis of miRNAs and the proteome highlighted a regulatory module between miRNAs and proteins, which, to a certain extent, may contribute to a better understanding of hepatic lipid metabolism disorders in SCH mice.
亚临床甲状腺功能减退症（SCH）因其患病率不断上升以及包括心血管疾病和非酒精性脂肪性肝病（NAFLD）在内的潜在不良影响，正成为一个全球性的健康问题。然而，SCH与NAFLD之间的关联仍存在争议。据报道，微小RNA（miRNA/miR）与脂质代谢紊乱有关；然而，miRNA如何调节SCH小鼠的肝脏脂质代谢仍不清楚。本研究调查了通过在小鼠中给予甲巯咪唑16周所建立的SCH小鼠模型中的miRNA变化和蛋白质组谱。接下来，使用逆转录定量聚合酶链反应和iTRAQ标记技术，对SCH（n = 9）和对照（n = 7）小鼠肝脏标本中对肝脏脂质代谢至关重要的17种miRNA和蛋白质组进行了研究。还使用TargetScan和miRanda对miRNA的潜在靶标进行了预测。与对照小鼠相比，SCH小鼠肝脏组织中有8种miRNA和36种蛋白质表达存在显著差异。此外，还鉴定出了一个由3种miRNA（miR-34a-5p、miR-24-3p和miR-130a-3p）和4种蛋白质（硫氧还蛋白、硒结合蛋白2、延伸因子1β和 prosaposin）组成的调控模块。总体而言，对miRNA和蛋白质组的综合分析突出了miRNA与蛋白质之间的调控模块，这在一定程度上可能有助于更好地理解SCH小鼠的肝脏脂质代谢紊乱。
