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Abstract: FR-PO974

Disruption of Annexin A2 Protects Against Obstruction-Induced Kidney Fibrosis and Inflammation

Session Information

  • CKD: Pathobiology - I
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms


  • Lin, Ling, Penn State College of Medicine, Hershey, Pennsylvania, United States
  • Hu, Kebin, Penn State College of Medicine, Hershey, Pennsylvania, United States

Annexin A2, a member of the Ca2+- and phospholipid-binding protein family, forms the heterotetramer through binding with S100A10, and acts as a cell surface receptor for tissue plasminogen activator (tPA) and plasminogen. It regulates fibrinolysis and hemostasis; and has been implicated in the pathogenesis of cardiovascular diseases and cancers. However, little is known regarding the role of annexin A2 in chronic kidney disease (CKD). Our previous in vitro work has shown that annexin A2 mediates NF-κB activation and promotes macrophage M2 to M1 phenotypic change, suggesting a critical role of annexin A2 in kidney fibrogenesis and inflammation.


We induced a classic CKD model, unilateral ureteral obstruction (UUO), in wildtype C57BL/6 mice and examined the renal expression of annexin A2 during the course of CKD. We also induced UUO in the novel annexin A2 knockout mice and their wildtype controls and evaluated the renal fibrosis and inflammation in these mice.


It was found that expression of annexin A2 was dramatically induced in the obstructed kidneys, as early as 3 days after UUO; and the upregulation continued up to 14 days after UUO. With the progression of kidney fibrosis, as indicated by increased fibronectin deposition in a time-dependent manner, annexin A2 was dramatically induced, and its induction correlated with the content of kidney fibrosis. Intriguingly, double immune staining analysis found that annexin A2 was dramatically induced in the renal interstitium, primarily in F4/80 positive macrophages. We further found that, after obstructive injury, annexin A2 knockout mice displayed significantly reduced tubular epithelial damage and dramatically decreased deposition of matrix components such as collagen and fibronectin than that of their littermates. Additionally, immunostaining showed that obstruction-induced infiltration of F4/80-positive macrophages was alleviated in the fibrotic kidneys from annexin A2 knockout mice.


Thus, it is clear that annexin A2 promotes kidney fibrosis and macrophage infiltration after obstructive injury.


  • NIDDK Support