背景:WNT/β-catenin系统是进化上保守的信号通路,在胚胎发生过程中在形态发生和细胞组织形成中起着至关重要的作用。虽然通常在成年期受到抑制,它可以在器官损伤和再生过程中重新激活。急性肾损伤后WNT/β-catenin通路的瞬时激活刺激组织再生,而持续(不受控制)的激活可以促进慢性肾脏病(CKD)的发展。CKD-MBD是一种由CKD引起的全身矿物质和骨代谢紊乱的临床综合征,以骨矿物质代谢异常和/或骨外钙化为特征,以及与CKD相关的心血管疾病,包括血管僵硬和钙化。
目的:本文旨在全面综述WNT/β-catenin信号通路与CKD-MBD的关系。专注于它的组成部分,调节分子,和监管机制。此外,这篇综述强调了在CKD-MBD治疗中使用小分子化合物靶向WNT/β-catenin信号通路的挑战和机遇。
方法:我们使用各种科学数据库进行了全面的文献综述,包括PubMed,Scopus,和WebofScience,确定相关文章。我们搜索了讨论WNT/β-catenin信号通路的文章,CKD-MBD,和他们的关系。我们还回顾了讨论WNT/β-catenin信号通路成分的文章,它的调节分子,和监管机制。
结果:WNT/β-catenin信号通路通过促进血管钙化和骨矿物质代谢紊乱在CKD-MBD中起关键作用。该途径的组成部分包括WNT配体,卷曲受体,和LRP5/6共受体,其启动导致β-连环蛋白激活的下游信号级联。几种调节分子,包括GSK-3β,APC,和Axin,调节β-连环蛋白激活。WNT/β-catenin信号通路也与其他信号通路相互作用,例如BMP途径,调节CKD-MBD。
结论:WNT/β-catenin信号通路是CKD-MBD的潜在治疗靶点。靶向该途径的组分或调节分子的小分子化合物可以提供治疗CKD-MBD的有希望的方法。然而,需要更多的研究来确定安全有效的化合物,并确定最佳剂量和治疗方案.
BACKGROUND: The WNT/β-catenin system is an evolutionarily conserved signaling pathway that plays a crucial role in morphogenesis and cell tissue formation during embryogenesis. Although usually suppressed in adulthood, it can be reactivated during organ damage and regeneration. Transient activation of the WNT/β-catenin pathway stimulates tissue regeneration after acute kidney injury, while persistent (uncontrolled) activation can promote the development of chronic kidney disease (CKD). CKD-MBD is a clinical syndrome that develops with systemic mineral and bone metabolism disorders caused by CKD, characterized by abnormal bone mineral metabolism and/or extraosseous calcification, as well as cardiovascular disease associated with CKD, including vascular stiffness and calcification.
OBJECTIVE: This paper aims to comprehensively review the WNT/β-catenin signaling pathway in relation to CKD-MBD, focusing on its components, regulatory molecules, and regulatory mechanisms. Additionally, this review highlights the challenges and opportunities for using small molecular compounds to target the WNT/β-catenin signaling pathway in CKD-MBD therapy.
METHODS: We conducted a comprehensive literature review using various scientific databases, including PubMed, Scopus, and Web of Science, to identify relevant articles. We searched for articles that discussed the WNT/β-catenin signaling pathway, CKD-MBD, and their relationship. We also reviewed articles that discussed the components of the WNT/β-catenin signaling pathway, its regulatory molecules, and regulatory mechanisms.
RESULTS: The WNT/β-catenin signaling pathway plays a crucial role in CKD-MBD by promoting vascular calcification and bone mineral metabolism disorders. The pathway\'s components include WNT ligands, Frizzled receptors, and LRP5/6 co-receptors, which initiate downstream signaling cascades leading to the activation of β-catenin. Several regulatory molecules, including GSK-3β, APC, and Axin, modulate β-catenin activation. The WNT/β-catenin signaling pathway also interacts with other signaling pathways, such as the BMP pathway, to regulate CKD-MBD.
CONCLUSIONS: The WNT/β-catenin signaling pathway is a potential therapeutic target for CKD-MBD. Small molecular compounds that target the components or regulatory molecules of the pathway may provide a promising approach to treat CKD-MBD. However, more research is needed to identify safe and effective compounds and to determine the optimal dosages and treatment regimens.