N ‐myc downstream‐regulated gene 1 is involved in the regulation of cystogenesis in transgenic mice overexpressing human PKD 2 gene

Autosomal dominant polycystic kidney disease ( ADPKD ) is an inheritable and progressive kidney disease featured by the formation of fluid‐filled cysts. In a previous study, transgenic mice overexpressing human PKD 2 gene were produced as an ADPKD animal model. To select genes controlled by PKD 2, 2 DE was performed using kidney tissues of 12‐ and 18‐month‐old transgenic mice. The protein localization was detected by immunohistochemistry, and 3 D culture was utilized to observe in vitro cystogenesis. As a result, N ‐myc downstream‐regulated gene 1 ( NDRG 1 ) was chosen as a candidate regulator gene of cystogenesis. NDRG 1 is an intracellular protein involved in cellular proliferation and differentiation. This gene was expressed much higher in the kidney of h PKD 2 TG mice. Also, the high level of NDRG 1 protein was detected in the cyst lining epithelial cells. The hypothesis that PKD 2 gene regulates NDRG 1 expression was supported, and NDRG 1 knockdown resulted in attenuation of cyst growth in vitro. Furthermore, NDRG 1 knockdown suppressed cellular growth in mouse inner medullary collecting duct‐3 cells. We found that early growth response 1, a transcription factor that binds to the NDRG 1 promoter, was mediated in the NDRG 1 expression regulation by PKD 2 . In this study, we found the novel gene that was involved in cystogenesis, which will provide the new insight in ADPKD .