Epigenetics in autosomal dominant polycystic kidney disease.

Biochim Biophys Acta Mol Basis Dis

Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China; Department of Medicine, Rhode Island Hospital and Alpert Medical School, Brown University, Providence, RI, USA. Electronic address:

Published: January 2025

Autosomal dominant polycystic kidney disease (ADPKD) is the fourth leading cause of end-stage renal disease, contributing substantially to patient morbidity, mortality, and healthcare system strain. Emerging research highlights a pivotal role of epigenetics in ADPKD's pathophysiology, where mechanisms like DNA methylation, histone modifications, and non-coding RNA regulation significantly impact disease onset and progression. These epigenetic factors influence gene expression and regulate key processes involved in cyst formation and expansion, fibrosis, and inflammatory infiltration, thus accelerating ADPKD progression. Consequently, exploring epigenetic regulatory mechanisms presents a valuable pathway for developing novel therapeutic strategies and diagnostic biomarkers aimed at slowing or preventing ADPKD progression. This review systematically examines existing studies on epigenetic alterations-including DNA methylation, histone modification, and non-coding RNA regulation-in ADPKD patients, providing insights into gene expression changes and functions, and identifying potential drug targets for ADPKD treatment. CLINICAL SIGNIFICANCE: Autosomal dominant polycystic kidney disease (ADPKD) is the fourth leading cause of end-stage renal disease, causing significant morbidity, increasing patient mortality, and weakening the healthcare system. Further study on ADPKD has revealed that epigenetics plays an important role in the pathophysiological process of ADPKD. Epigenetics has a significant impact on the formation and progression of ADPKD through a variety of processes including DNA methylation, histone modification, and non-coding RNA. In addition to boosting cyst formation and proliferation, it induces cystic fibrosis and inflammatory cell infiltration, ultimately leading to a poor prognosis. This review summarizes the current understanding of the associated alterations in gene expression and function produced by epigenetic regulation in ADPKD, as well as potential treatment targets.

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http://dx.doi.org/10.1016/j.bbadis.2024.167652DOI Listing

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