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EZH2 inhibition or genetic ablation suppresses cyst growth in autosomal dominant polycystic kidney disease.


ABSTRACT:

Background

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a prevalent genetic disorder characterized by the formation of renal cysts leading to kidney failure. Despite known genetic underpinnings, the variability in disease progression suggests additional regulatory layers, including epigenetic modifications.

Methods

We utilized various ADPKD models, including Pkd1 and Ezh2 conditional knockout (Pkd1delta/delta:Ezh2delta/delta) mice, to explore the role of Enhancer of Zeste Homolog 2 (EZH2) in cystogenesis. Pharmacological inhibition of EZH2 was performed using GSK126 or EPZ-6438 across multiple models.

Results

EZH2 expression was significantly upregulated in Pkd1-/- cells, Pkd1delta/delta mice, and human ADPKD kidn

SUBMITTER: Lv J 

PROVIDER: S-EPMC11520870 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature