Abstract: TH-PO0218
Critical Role of Transcription Factor PU.1 in Regulating NLRP3 Inflammasome Signaling in Kidney Fibrosis
Session Information
- CKD: Mechanisms of Injury and Fibrosis - 1
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Jiao, Baihai, University of Connecticut School of Medicine, Farmington, Connecticut, United States
- Tran, Melanie, University of Connecticut School of Medicine, Farmington, Connecticut, United States
- Yang, Dong, University of Connecticut School of Medicine, Farmington, Connecticut, United States
- Wang, Yanlin, University of Connecticut School of Medicine, Farmington, Connecticut, United States
Background
Chronic kidney disease (CKD) is characterized by persistent inflammation and fibrosis. The NLRP3 inflammasome plays a central role in kidney injury, but the transcriptional regulation of inflammasome activation remains poorly understood. We investigated the role of the transcription factor PU.1 in regulating NLRP3 inflammasome signaling during kidney fibrosis.
Methods
Myeloid-specific PU.1 knockout mice were subjected to unilateral ureteral obstruction (UUO) and folic acid–induced nephropathy (FA) models to investigate the role of PU.1 in kidney fibrosis. Bone marrow–derived macrophages (BMDMs) and ChIP-seq analysis were used to examine the molecular mechanisms underlying PU.1-mediated regulation of NLRP3 inflammasome signaling.
Results
PU.1 expression was markedly increased in fibrotic mouse kidneys and human CKD kidneys. Myeloid-specific deletion of PU.1 reduced NLRP3 expression, suppressed caspase-1 activation, and decreased IL-1β and IL-18 production, thereby attenuating kidney inflammation and fibrosis. Mechanistically, ChIP analysis demonstrated direct binding of PU.1 to the NLRP3 promoter, promoting NLRP3 transcription and inflammasome activation in response to kidney injury.
Conclusion
These findings identify PU.1 as a key transcriptional regulator of NLRP3 inflammasome signaling in macrophages and suggest that PU.1 contributes to kidney inflammation and fibrosis during CKD progression.
Funding
- NIDDK Support