Kidney Week

Abstract: TH-PO0249

Endothelial Angiopoietin-2 Contributes to Early but Not Late Kidney Injury After Unilateral Ureteral Obstruction

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

• Luo, An Jie, National Taiwan University College of Medicine, Taipei City, Taiwan

An Jie Luo, PhD

• Chang, Fan-Chi, National Taiwan University Hospital, Taipei City, Taiwan

Fan-Chi Chang, MD, PhD

• Lin, Shuei-Liong, National Taiwan University College of Medicine, Taipei City, Taiwan

Shuei-Liong Lin, MD, PhD

Background

Chronic kidney disease (CKD) is characterized by persistent inflammation and fibrosis. Angiopoietin-2 has been associated with endothelial dysfunction and vascular inflammation; however, its endothelial-specific role in CKD remains unclear. This study investigated the effects of endothelial-derived angiopoietin-2 in unilateral ureteral obstruction (UUO)-induced CKD.

Methods

Endothelial cell-specific angiopoietin-2 knockout mice (Angpt2^ΔEC) and control mice underwent UUO or sham surgery. Mice were sacrificed on day 4 or day 14 after surgery to evaluate early- and late-stage CKD, respectively. Kidney tissues were harvested for quantitative PCR (qPCR), protein analysis, endothelial cell isolation, and immunofluorescence staining for F4/80⁺ macrophages.

Results

In early UUO-induced CKD, Angpt1 expression showed no significant difference between groups. In contrast, Angpt2 expression was significantly increased after UUO in control mice, whereas Angpt2^ΔEC mice exhibited significantly lower renal Angpt2 mRNA and protein levels, indicating effective endothelial-specific deletion. Expression of the pro-inflammatory genes Ccl2 and Cx3cl1, as well as the adhesion molecules Icam1 and Vcam1, was significantly reduced in Angpt2^ΔEC kidneys compared with controls on day 4 after UUO. Immunofluorescence staining also demonstrated decreased F4/80⁺ macrophage infiltration in Angpt2^ΔEC mice. Furthermore, isolated renal endothelial cells from Angpt2^ΔEC mice showed significantly reduced Cx3cl1 and Icam1 expression, suggesting that endothelial-derived angiopoietin-2 promotes inflammatory activation during early CKD.
At day 14 after UUO, pro-inflammatory, adhesion molecule, and pro-fibrotic genes were markedly elevated in both groups; however, no significant differences were observed between Angpt2^ΔEC and control mice.

Conclusion

These findings demonstrate that endothelial-derived angiopoietin-2 plays an important role in early CKD-associated inflammation. Endothelial-specific deletion of angiopoietin-2 attenuated inflammatory gene expression and macrophage infiltration during early UUO injury, but this protective effect was diminished in late-stage CKD. These results suggest that angiopoietin-2 contributes to CKD progression in a stage-dependent manner and may serve as a therapeutic target in early CKD.