#3971 INJURY INDUCED RENAL FIBROSIS PROMOTES CYSTOGENESIS AND CYST GROWTH IN ADULT MICE WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Abstract Background and Aims Acute kidney injury (AKI) is not a merely transient event, which can lead to subsequent progression chronic disease (CKD). Autosomal dominant polycystic (ADPKD) the most frequent inherited caused by mutations in PKD1 or PKD2 gene. Previous studies showed that acute injuries promote cystogenesis adult mice with ADPKD. Fibrosis hallmark of AKI CKD (AKI-CKD) transition, positively correlated renal cyst growth humans. All these data imply role AKI-CKD transition ADPKD.In this study, we aimed determine Method We established model toxic surgical injuries, Pkd gene inactivation was performed different time point transition. The fibrosis shown Western blotting analysis induced model. Results before after both induce formation Pkd1 Pkd2 mice, extent initial level three hits (injury inactivation). Inactivation at recovery stage surgery less mice. Enhanced repeated accelerated further speed early decided baseline fibrosis. Finally, conditional knockout Ezh2 attenuated Conclusion Fibrotic responses driving force for kidneys inhibition through targeting EZH2 might be new therapeutic strategy