Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea.
Proteomics. 2013 Jan;13(1):134-41. doi: 10.1002/pmic.201200248.
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.
常染色体显性多囊肾病 (ADPKD) 是一种遗传性进行性肾脏疾病，其特征是形成充满液体的囊肿。在之前的一项研究中，产生了过表达人 PKD2 基因的转基因小鼠作为 ADPKD 动物模型。为了选择受 PKD2 控制的基因，使用 12 个月和 18 个月大的转基因小鼠的肾脏组织进行了 2DE。通过免疫组织化学检测蛋白质定位，并利用 3D 培养观察体外囊泡发生。结果，N-myc 下游调节基因 1 (NDRG1) 被选为囊泡发生的候选调节基因。NDRG1 是一种参与细胞增殖和分化的细胞内蛋白。该基因在 hPKD2 TG 小鼠的肾脏中表达水平更高。此外，在囊泡衬里上皮细胞中也检测到高水平的 NDRG1 蛋白。PKD2 基因调节 NDRG1 表达的假设得到支持，并且 NDRG1 敲低导致体外囊泡生长减弱。此外，NDRG1 敲低抑制了小鼠内髓集合管-3 细胞的细胞生长。我们发现，早期生长反应 1 是一种与 NDRG1 启动子结合的转录因子，它介导了 PKD2 对 NDRG1 表达的调节。在这项研究中，我们发现了参与囊泡发生的新基因，这将为 ADPKD 提供新的见解。
