Obesity Research Center, Proteomics Resource Unit, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia.
Department of Medicine, College of Medicine and King Saud Medical City, King Saud University, P.O. Box 2925 (98), Riyadh 11461, Saudi Arabia.
Molecules. 2021 Apr 1;26(7):1991. doi: 10.3390/molecules26071991.
Hyperthyroidism, which is characterized by increased circulating thyroid hormone levels, alters the body's metabolic and systemic hemodynamic balance and directly influences renal function. In this study, the urinary proteome of patients with hyperthyroidism was characterized using an untargeted proteomic approach with network analysis. Urine samples were collected from nine age-matched patients before and after carbimazole treatment. Differences in the abundance of urinary proteins between hyperthyroid and euthyroid states were determined using a 2D-DIGE coupled to MALDI-TOF mass spectrometry. Alterations in the abundance of urinary proteins, analyzed via Progenesis software, revealed a statistically significant difference in abundance in a total of 40 spots corresponding to 32 proteins, 25 up and 7 down (≥1.5-fold change, ANOVA, ≤ 0.05). The proteins identified in the study are known to regulate processes associated with cellular metabolism, transport, and acute phase response. The notable upregulated urinary proteins were serotransferrin, transthyretin, serum albumin, ceruloplasmin, alpha-1B-glycoprotein, syntenin-1, and glutaminyl peptide cyclotransferase, whereas the three notable downregulated proteins were plasma kallikrein, protein glutamine gamma-glutamyl transferase, and serpin B3 (SERPINB3). Bioinformatic analysis using ingenuity pathway analysis (IPA) identified the dysregulation of pathways associated with cellular compromise, inflammatory response, cellular assembly, and organization and identified the involvement of the APP and AKT signaling pathways via their interactions with interleukins as the central nodes.
甲状腺功能亢进症，其特征是循环甲状腺激素水平升高，改变了身体的代谢和全身血液动力学平衡，并直接影响肾功能。在这项研究中，使用靶向蛋白质组学方法和网络分析来描述甲状腺功能亢进症患者的尿液蛋白质组。收集了 9 名年龄匹配的患者在卡比马唑治疗前后的尿液样本。使用 2D-DIGE 结合 MALDI-TOF 质谱法确定甲状腺功能亢进和甲状腺功能正常状态下尿液蛋白质丰度的差异。通过 Progenesis 软件分析尿液蛋白质丰度的变化，揭示了在总共 40 个斑点中存在统计学上显著差异，对应于 32 种蛋白质，25 种上调和 7 种下调（≥1.5 倍变化，ANOVA，≤0.05）。该研究中鉴定的蛋白质已知调节与细胞代谢、运输和急性期反应相关的过程。显著上调的尿液蛋白质有转铁蛋白、转甲状腺素蛋白、血清白蛋白、铜蓝蛋白、α-1B-糖蛋白、衔接蛋白-1 和谷氨酰肽环转移酶，而下调的三种显著蛋白质是血浆激肽释放酶、蛋白质谷氨酰胺γ-谷氨酰转移酶和丝氨酸蛋白酶 B3（SERPINB3）。使用 ingenuity 通路分析（IPA）进行的生物信息学分析确定了与细胞损伤、炎症反应、细胞组装和组织以及 APP 和 AKT 信号通路的失调相关的途径，通过它们与白细胞介素的相互作用确定了它们的参与作为中心节点。
