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Abstract: FR-PO286

Injury-Induced Renal Fibrosis Promotes Cystogenesis and Cyst Growth in Adult Mice With Autosomal Dominant Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1101 Genetic Diseases of the Kidneys: Cystic


  • Wang, Yanzhe, Shuguang Hospital, ShangHai, China
  • Wu, Ming, Shuguang Hospital, ShangHai, China
  • Ye, Chaoyang, Shuguang Hospital, ShangHai, China

Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited kidney disease caused by mutations in PKD1 or PKD2 gene. Enhanced fibrosis is correlated with the accelerated renal function decline and kidney growth in the late stage of ADPKD patients. However, the role of fibrosis in ADPKD remains unclear.


We established renal fibrosis by toxic (aristolochic acid I, AAI; 1,2-dichlorovinyl-cysteine, DCVC) or surgical (unilateral ischemia reperfusion injury, UIRI) injuries which was prior to Pkd gene inactivation in adult mice.


Here we showed that renal cysts were induced in adult Pkd1 or Pkd2 mice with pre-established renal fibrosis. Recovery of renal fibrosis at three weeks after UIRI retarded cystogenesis in Pkd1 mice. Enhanced renal fibrosis by repeated toxic injuries accelerated renal cyst growth in Pkd1 mice. We further showed that the rate of cyst formation at the early stage of adult Pkd1 mice was decided by the baseline level of renal fibrosis. Finally, we showed that conditional knockout of EZH2 attenuated renal fibrosis and cyst growth in Pkd1 mice with established renal fibrosis.


We conclude that fibrosis is a driving force for renal cyst formation and growth in adult kidneys and inhibition of renal fibrosis through targeting EZH2 might be a new therapeutic strategy for ADPKD.