Abstract: TH-OR011
Distinct Roles of Endothelial and Tubular Angiopoietin-2 in CKD Progression: Inflammation, Fibrosis, and Metabolic Reprogramming
Session Information
- CKD: Exploring Intertwined Mechanisms of Disease Progression
November 06, 2025 | Location: Room 362A, Convention Center
Abstract Time: 04:40 PM - 04:50 PM
Category: CKD (Non-Dialysis)
- 2303 CKD (Non-Dialysis): Mechanisms
Authors
- Chang, Fan-Chi, National Taiwan University Hospital, Taipei City, Taiwan
- Luo, An Jie, National Taiwan University College of Medicine, Taipei City, Taiwan
- Gau, Tyng-shiuan, National Taiwan University Hospital, Taipei City, Taiwan
- Tsai, Ming-Tsun, Taipei Veterans General Hospital, Taipei City, Taiwan
- Li, Szu-Yuan, Taipei Veterans General Hospital, Taipei City, Taiwan
- Lin, Shuei-Liong, National Taiwan University Hospital, Taipei City, Taiwan
Background
Angiopoietin-2 (Angpt2), a context-dependent vascular growth factor, is implicated in chronic kidney disease (CKD) progression, yet its cell-specific roles remain unclear.
Methods
Kidney ANGPT2 expression was analyzed in 127 biopsy specimens. In situ hybridization was used to localize ANGPT2 expression. In murine models of adenine-induced CKD, we evaluated global, EC-, and TEC-specific Angpt2 knockout mice. Kidney function, histopathology, immunofluorescence, μCT, and transcriptomic analyses were used to delineate cell-type–specific mechanisms.
Results
In CKD patients, elevated kidney ANGPT2 correlated with reduced eGFR, increased fibrosis, and poor renal outcomes. Global Angpt2 deletion in mice improved kidney function, reduced fibrosis, macrophage infiltration, and vascular rarefaction. RNA-seq revealed suppression of pro-inflammatory and pro-fibrotic pathways alongside marked upregulation of metabolic programs, particularly fatty acid β-oxidation and peroxisomal lipid metabolism. EC-specific Angpt2 deletion suppressed early-stage CKD inflammation by downregulating chemokines and adhesion molecules but did not prevent late-stage damage. TEC-specific Angpt2 deletion mitigated tubulointerstitial injury, vascular rarefaction, and fibrosis in advanced CKD. Mechanistically, angpt2-actived ECs promoted macrophage infiltration and extracellular matrix deposition through distinct endothelial and tubular pathways.
Conclusion
Angiopoietin-2 plays a dual-stage, cell-specific role in CKD pathogenesis: EC-derived Angpt2 drives early inflammation, while TEC-derived Angpt2 sustains fibrosis and metabolic dysfunction in advanced disease. Targeting Angpt2 may offer a promising therapeutic strategy addressing both immune and metabolic dysregulation in CKD.