Kidney Week

Abstract: FR-PO1203

Annexin-A2 Contributes to Tubulointerstitial Fibrosis in a Murine Model of CKD

Session Information

• CKD: Mechanisms, AKI, and Beyond - 2
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Yung, Susan, Department of Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

Susan Yung, PhD

• Xu, Yuesong, Department of Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

Yuesong Xu, MS, MSc

• Wu, Haoyuan, Department of Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

Haoyuan Wu

• Wong, Cheuk Yin, Department of Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

Cheuk Yin Wong, PhD

• Chan, Tak Mao Daniel, Department of Medicine, The University of Hong Kong, Hong Kong SAR, Hong Kong

Tak Mao Daniel Chan, MD, FASN

Background

Tubulo-interstitial fibrosis is considered the predominant pathogenic process in chronic kidney disease (CKD) progression to end-stage kidney disease. Emerging evidence suggests that annexin-A2 (AnxA2), a Ca²⁺-dependent phospholipid-binding protein, contributes to fibrotic processes, but its role in kidney fibrosis remains obscure. This study investigated the role of AnxA2 in CKD.

Methods

CKD was induced in male wild-type (WT) and AnxA2 knockout (KO) mice by feeding with casein-based chow containing 0.2% adenine for 12 weeks, after which time kidneys were harvested to assess the expression of mediators of kidney injury, inflammation and fibrosis. Mice fed casein-based chow served as non-CKD controls. The relationship between tubulo-interstitial anxa2 expression and kidney function in CKD patients was investigated using publicly available transcriptomics datasets from NephroSeq.

Results

Tubulo-interstitial AnxA2 expression increased 11.14 ± 2.11-fold in WT CKD mice compared with non-CKD WT mice, and this was accompanied by development of proteinuria, tubular atrophy, protein cast formation, influx of immune cells, and increased expression of TGF-β1, α-smooth muscle actin, fibronectin, collagen and KIM-1. AnxA2 KO mice with CKD showed less severe histopathological abnormalities, reduced proteinuria and decreased expression of mediators of fibrosis compared to WT CKD mice. Tubulo-interstitial anxa2 gene expression was increased by 3.61-,1.95-, and 1.84-fold in patients with diabetic nephropathy, ANCA-vasculitis and lupus nephritis respectively compared to healthy controls (p<0.001, for all), especially in patients with nephrotic syndrome, and correlated with serum creatinine level (r = 0.63, p<0.001) and inversely correlated with GRF (r = -0.68, p<0.01). Tubulo-interstitial anxa2 expression also correlated with col1a1 (r = 0.63, p<0.01) and fn1 (r = 0.53, p<0.01) expression, and the percentage of interstitial fibrosis and tubular atrophy (r = 0.73, p<0.001) in CKD patients.

Conclusion

Our data suggest that AnxA2 may contribute to tubulo-interstitial fibrosis and kidney function deterioration in patients and mice with CKD.

Funding

• Government Support – Non-U.S.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025vnqxhn92