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Abstract: FR-PO1068

Annexin A2 Promotes Tubular Epithelial Trans-Differentiation and Kidney Fibrosis

Session Information

Category: CKD (Non-Dialysis)

  • 2303 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 is a Ca2+- and phospholipid-binding protein widely expressed in various cells and tissues. It acts as a cell surface receptor for tissue plasminogen activator (tPA) and plasminogen, regulating the homeostasis of blood coagulation, fibrinolysis and matrix degradation. However, its role in kidney fibrosis remains largely unknown. 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.


Unilateral ureteral obstruction (UUO) was induced in a novel annexin A2 knockout mice and their wildtype counterparts. Renal histology was evaluated. Kidney fibrosis, renal annexin A2 level, and epithelial transdifferentiation were examined in these mice.


Annexin A2 was dramatically induced in the obstruction-induced fibrotic kidneys in a time-dependent manner, and its induction correlated with the extent of fibrotic injury as indicated by fibronectin deposition. Intriguingly, double immune staining analysis found that annexin A2 was dramatically induced in the interstitial F4/80-positive macrophages. It was 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 control littermates. Additionally, obstruction-induced epithelial transdifferentiation was significantly reduced in annexin A2 knockout mice as indicated by increase of Ecadherin and decrease of de novo induction of αSMA.


Thus, it is clear that annexin A2 promotes epithelial transdifferentiation and kidney fibrosis after obstructive injury. Additionally, our results indicate a role of macrophages in annexin A2-mediated epithelial damage and transdifferentiation.


  • Other U.S. Government Support