常染色体显性多囊肾病 (ADPKD) 是一种常见的遗传性疾病，主要由 Pkd1 (PC1) 突变引起，占 ADPKD 病例的大多数。这些突变导致肾脏和其他器官形成囊肿，最终导致肾衰竭。不幸的是，目前还没有针对这种疾病的预防性治疗方法。在这项研究中，我们利用 Pkd1 敲低小鼠和细胞来研究 O-GlcNAc 基化在 PKD 进展中的潜在参与。此外，我们还检测了 O-GlcNAcase (OGA) 抑制剂硫美特 G 对 PKD 小鼠的影响。我们的研究结果表明，在 Pkd1 沉默的肾组织中，O-GlcNAc 酰化和 OGT（O-GlcNAc 转移酶）均下调。老鼠。此外，O-GlcNAc 酰化可调节 PC1 C 端胞质尾 (CTT) 的稳定性和功能。用噻美特 G 治疗 PKD 小鼠，导致这些动物的肾细胞生成减少。这些结果突出了 O-GlcNAcNAc 化在 PKD 囊肿形成发展中的独特作用，并提出其作为治疗 PKD 的潜在治疗靶点。版权所有 © 2023，国际抗癌研究所（George J. Delinasios 博士），保留所有权利。

Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent genetic disorder primarily caused by mutations in Pkd1 (PC1), which account for the majority of ADPKD cases. These mutations contribute to the formation of cysts in the kidneys and other organs, ultimately leading to renal failure. Unfortunately, there are currently no available preventive treatments for this disease.In this study, we utilized Pkd1-knockdown mice and cells to investigate the potential involvement of O-GlcNAcylation in the progression of PKD. Additionally, we examined the effects of thiamet G, an inhibitor of O-GlcNAcase (OGA), on PKD mice.Our findings indicate that both O-GlcNAcylation and OGT (O-GlcNAc transferase) were downregulated in the renal tissues of Pkd1-silenced mice. Furthermore, O-GlcNAcylation was shown to regulate the stability and function of the C-terminal cytoplasmic tail (CTT) of PC1. Treatment of PKD mice with thiamet G resulted in a reduction of renal cytogenesis in these animals.These results highlight the unique role of O-GlcNAcylation in the development of cyst formation in PKD and propose it as a potential therapeutic target for the treatment of PKD.Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.