EGR1 Nuclear Condensates Promote Renal Cyst Development in Polycystic Kidney Disease - PubMed
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- #phase separation
- #EGR1
- #ADPKD
- EGR1 nuclear condensates play a critical role in renal cyst development in Autosomal Dominant Polycystic Kidney Disease (ADPKD).
- EGR1 is activated by cAMP-PKA and MAPK signaling pathways, similar to mechanisms in tumor cell proliferation.
- High expression and nuclear condensates of EGR1 were found in human ADPKD renal cyst epithelial cells and PKD mouse kidney tissue.
- Pharmacological inhibition of EGR1 slowed cyst enlargement in various ADPKD models (in vitro, ex vivo, and in vivo).
- EGR1 forms nuclear condensates with YAP1 and CBP via phase separation, leading to transcriptional activation of cell-cycle-related genes (e.g., CCND1, CCNE1, CDK4/6).
- Disruption of EGR1 phase separation significantly reduced cyst growth in forskolin-induced 3D spheroid and MDCK cyst models.