Abstract: FR-PO0154
NINJ1-Mediated Plasma Membrane Rupture and Release of HMGB1 Contribute to AKI-to-CKD Transition
Session Information
- AKI: Mechanisms - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Ye, Keng, Department of Nephrology, Blood Purification Research Center, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China
- Chen, Zhimin, Department of Nephrology, Blood Purification Research Center, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China
- Ma, Huabin, Central Laboratory, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China
- Xu, Yanfang, Department of Nephrology, Blood Purification Research Center, the First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China
Background
It has been found that Ninjurin-1(NINJ1) plays an important role in the plasma membrane rupture followed by damage-associated molecular patterns (DAMPs) release. HMGB1 has been reported as a regulator of inflammatory cells and a major DAMP released during both acute kidney injury (AKI) and chronic kidney disease (CKD). Thereafter we hypothesize that NINJ1-mediated tubular epithelial cell PMR releases high mobility group box 1 (HMGB1), resulting in macrophage polarization and neutrophil extracellular traps (NETs) formation synergistically contributing to the progression of AKI-CKD transition.
Methods
Using a murine model of FA-induced nephropathy, renal tubular specific deletion of Ninj1 mice (Ninj1fl/flKspcre) and their wild-type littermate control mice (Ninj1wt/wtKspcre) were administered with a single intraperitoneal injection of 225 mg/kg folic acid. Evaluation was conducted on tubular injury, renal fibrosis and inflammatory cell infiltration. In vitro studies involved isolation and culture of renal proximal tubular epithelial cells (RTECs) to investigate NINJ1-mediated HMGB1 release, bone marrow-derived macrophages to observe macrophage polarization and macrophage-to-myofibroblast transition, and neutrophils to explore NETs formation.
Results
Targeted deletion of Ninj1 in renal tubules significantly mitigated FA-induced AKI-CKD transition by suppressing HMGB1 release, inflammation and fibrosis in vivo. In vitro studies demonstrated that HMGB1 release from RTECs PMR mediated by NINJ1 oligomerization, which regulated the level of macrophage polarization, macrophage-to-myofibroblast transition and NETs formation, consequently coordinating to enhance renal tubular epithelial cell death.
Conclusion
Our findings elucidate the pivotal role of NINJ1-dependent renal tubular epithelial PMR followed by HMGB1release in the progression of AKI-CKD transition, providing novel insights for its prevention and therapeutic targets.