Kokkinopoulou Ioanna, Papadopoulou Anna
Laboratory of Clinical Biochemistry, University General Hospital 'Attikon', Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece.
Metabolites. 2025 May 26;15(6):351. doi: 10.3390/metabo15060351.
Thioredoxin-interacting protein (TXNIP) is a major inhibitor of the thioredoxin (TRX) antioxidant system and an important player in the development and aggravation of intracellular oxidative stress. Although first recognized as a metabolic regulator, recent studies have identified the multifaceted role of this protein in other molecular pathways involving inflammation, apoptosis, and glucose metabolism. : This review aims to highlight the importance of TXNIP in diabetes-related pathophysiology and explore the existing evidence regarding TXNIP's role in GDM-associated pathogenetic mechanisms, revealing common regulatory pathways. Among other complex diseases, TXNIP has been found upregulated in diabetic pancreatic beta cells, thus contributing to diabetes pathogenesis and its related complications. In addition, depletion of TXNIP has been shown to decrease the negative consequences of excessive stress in various cellular systems and diseases, pointing towards a potential therapeutic target. In line with these findings, TXNIP has been investigated in the pathogenesis of Gestational Diabetes Mellitus (GDM), a common pregnancy complication affecting the mother and the neonate. Overexpression of TXNIP has been found in GDM placentas or trophoblast cell lines mimicking GDM conditions and has been associated with key dysregulated mechanisms of GDM pathophysiology, like oxidative stress, inflammation, apoptosis, impaired autophagy, altered trophoblast behavior, and placental morphology. Interestingly, TXNIP has been found upregulated in GDM maternal serum and downregulated in umbilical cord blood, indicating potential compensatory protective mechanisms to GDM-related oxidative stress. Due to its contribution to the regulation of critical cellular processes such as inflammation, metabolism, and apoptosis, TXNIP finds its place in the pathophysiology of gestational diabetes through a currently limited number of scientific reports.
硫氧还蛋白相互作用蛋白（TXNIP）是硫氧还蛋白（TRX）抗氧化系统的主要抑制剂，也是细胞内氧化应激发展和加剧的重要参与者。尽管最初被认为是一种代谢调节因子，但最近的研究已经确定了该蛋白在涉及炎症、细胞凋亡和葡萄糖代谢的其他分子途径中的多方面作用。 本综述旨在强调TXNIP在糖尿病相关病理生理学中的重要性，并探讨关于TXNIP在妊娠期糖尿病（GDM）相关致病机制中作用的现有证据，揭示共同的调节途径。在其他复杂疾病中，已发现TXNIP在糖尿病胰腺β细胞中上调，从而导致糖尿病发病及其相关并发症。此外，已证明TXNIP的缺失可减少各种细胞系统和疾病中过度应激的负面影响，这表明它是一个潜在的治疗靶点。与这些发现一致，TXNIP已在妊娠期糖尿病（GDM）的发病机制中得到研究，GDM是一种影响母亲和新生儿的常见妊娠并发症。在模拟GDM条件的GDM胎盘或滋养层细胞系中发现TXNIP过表达，并且它与GDM病理生理学的关键失调机制有关，如氧化应激、炎症、细胞凋亡、自噬受损、滋养层细胞行为改变和胎盘形态。有趣的是，已发现TXNIP在GDM母体血清中上调，而在脐带血中下调，这表明存在针对GDM相关氧化应激的潜在代偿性保护机制。由于TXNIP对炎症、代谢和细胞凋亡等关键细胞过程的调节作用，通过目前数量有限的科学报告，TXNIP在妊娠期糖尿病的病理生理学中占有一席之地。
