title: N-myc downstream-regulated gene 1 is involved in the regulation of cystogenesis in transgenic mice overexpressing human PKD2 gene.
abstract: 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 PKD2 gene were produced as an ADPKD animal model. To select genes controlled by PKD2, 2DE was performed using kidney tissues of 12- and 18-month-old transgenic mice. The protein localization was detected by immunohistochemistry, and 3D culture was utilized to observe in vitro cystogenesis. As a result, N-myc downstream-regulated gene 1 (NDRG1) was chosen as a candidate regulator gene of cystogenesis. NDRG1 is an intracellular protein involved in cellular proliferation and differentiation. This gene was expressed much higher in the kidney of hPKD2 TG mice. Also, the high level of NDRG1 protein was detected in the cyst lining epithelial cells. The hypothesis that PKD2 gene regulates NDRG1 expression was supported, and NDRG1 knockdown resulted in attenuation of cyst growth in vitro. Furthermore, NDRG1 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 NDRG1 promoter, was mediated in the NDRG1 expression regulation by PKD2. In this study, we found the novel gene that was involved in cystogenesis, which will provide the new insight in ADPKD.
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
authors.forename: Bo Hye
authors.initials: BH
authors.lastname: Kim
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Park
authors.forename: Kyung Hyun
authors.initials: KH
authors.lastname: Yoo
authors.forename: Kyung Mi
authors.initials: KM
authors.lastname: Choi
authors.forename: Yona
authors.initials: Y
authors.lastname: Kim
authors.forename: Je kyung
authors.initials: Jk
authors.lastname: Seong
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D020420:Cyst Fluid / Q000378:metabolism; D003560:Cysts / Q000235:genetics / Q000378:metabolism; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050396:TRPP Cation Channels / Q000235:genetics / Q000378:metabolism; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D051766:Early Growth Response Protein 1; D047908:Intracellular Signaling Peptides and Proteins; D050396:TRPP Cation Channels; D000099259:N-myc Downstream-Regulated Gene 1 Protein; C486109:Egr1 protein, mouse