Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Department of Surgery, Daejeon Eulji Medical Center, Eulji University, Daejeon, South Korea.
Front Endocrinol (Lausanne). 2022 Aug 15;13:966644. doi: 10.3389/fendo.2022.966644. eCollection 2022.
The thyroid gland plays an essential role in the regulation of body energy expenditure to maintain metabolic homeostasis. However, to date, there are no studies investigating the morphological and functional changes of the thyroid gland due to mitochondrial stress in metabolic organs such as the liver. We used data from the Genotype-Tissue Expression portal to investigate RNA expression patterns of the thyroid gland according to the expression of growth differentiation factor 15 (GDF15) such as the muscles and liver. To verify the effect of hepatic GDF15 on the thyroid gland, we compared the morphological findings of the thyroid gland from liver-specific GDF15 transgenic mice to that of wild type mice. High GDF15 expression in the muscles and liver was associated with the upregulation of genes related to hypoxia, inflammation (TGF-α NFκB), apoptosis, and p53 pathway in thyroid glands. In addition, high hepatic GDF15 was related to epithelial mesenchymal transition and mTORC1 signaling. Electron microscopy for liver-specific GDF15 transgenic mice revealed short mitochondrial cristae length and small mitochondrial area, indicating reduced mitochondrial function. However, serum thyroid stimulating hormone (TSH) level was not significantly different. In our human cohort, those with a high serum GDF15 level showed high fasting glucose, alanine transaminase, and alkaline phosphatase but no difference in TSH, similar to the data from our mice model. Additionally, high serum GDF15 increased the risk of lymph node metastasis to lateral neck. The hepatic GDF15 affected thyroid morphogenesis a TSH-independent mechanism, affecting aggressive features of thyroid cancers.
甲状腺在调节身体能量消耗以维持代谢平衡方面起着至关重要的作用。然而，迄今为止，尚无研究探讨由于肝脏等代谢器官中线粒体应激导致甲状腺形态和功能的变化。我们使用 Genotype-Tissue Expression 门户的数据，根据生长分化因子 15（GDF15）在肌肉和肝脏等组织中的表达，研究甲状腺的 RNA 表达模式。为了验证肝 GDF15 对甲状腺的影响，我们比较了肝特异性 GDF15 转基因小鼠和野生型小鼠甲状腺的形态学发现。肌肉和肝脏中 GDF15 的高表达与甲状腺中与缺氧、炎症（TGF-αNFκB）、细胞凋亡和 p53 途径相关的基因上调有关。此外，高肝 GDF15 与上皮间质转化和 mTORC1 信号有关。肝特异性 GDF15 转基因小鼠的电子显微镜显示，线粒体嵴长度短，线粒体面积小，表明线粒体功能降低。然而，血清促甲状腺激素（TSH）水平没有显著差异。在我们的人类队列中，那些血清 GDF15 水平高的人表现出高空腹血糖、丙氨酸转氨酶和碱性磷酸酶，但 TSH 没有差异，与我们的小鼠模型数据相似。此外，高血清 GDF15 增加了向侧颈淋巴结转移的风险。肝 GDF15 通过 TSH 非依赖机制影响甲状腺形态发生，影响甲状腺癌的侵袭性特征。
