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The WNT/β-catenin system in chronic kidney disease-mineral bone disorder syndrome

  • Nephrology - Review
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

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.

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Data availability

Our study did not report any data.

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  1. Lingbo Zhang and Isaac Kumi Adu have equally contributed to this work.

Authors and Affiliations

  1. The School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, People’s Republic of China

    Lingbo Zhang & Isaac Kumi Adu

  2. Department of Internal Medicine, The Second Hospital of Jingzhou and the Affiliated Hospital of Hubei College of Chinese Medicine, Jingzhou, People’s Republic of China

    Isaac Kumi Adu, Haifeng Zhang & Jiancheng Wang

  3. Department of Internal Medicine, Kings and Queens University College and Teaching Hospital, Akosombo, Ghana

    Isaac Kumi Adu

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  1. Lingbo Zhang
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Zhang, L., Adu, I.K., Zhang, H. et al. The WNT/β-catenin system in chronic kidney disease-mineral bone disorder syndrome. Int Urol Nephrol 55, 2527–2538 (2023). https://doi.org/10.1007/s11255-023-03569-2

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