NS398 as a potential drug for autosomal-dominant polycystic kidney disease: Analysis using bioinformatics, and zebrafish and mouse models

Autor: Shoulian Zhou, Lili Fu, Sixiu Chen, Bo Yang, Linxi Huang, Qingzhou Zhang, Changlin Mei, Dechao Xu, Mengna Ruan, Zhiguo Mao
Rok vydání: 2021
Předmět:
cystogenesis
bioinformatics analysis
Biopsy
Autosomal dominant polycystic kidney disease
clear‐cell renal cell carcinoma
Biology
Bioinformatics
urologic and male genital diseases
Mice
Renal cell carcinoma
Databases
Genetic
Protein Interaction Mapping
medicine
Polycystic kidney disease
Animals
Humans
Cyclooxygenase Inhibitors
Genetic Predisposition to Disease
NS398
Gene
Zebrafish
Nitrobenzenes
Protein Kinase C
Sulfonamides
urogenital system
Gene Expression Profiling
Anti-Inflammatory Agents
Non-Steroidal
autosomal‐dominant polycystic kidney disease
Cancer
Computational Biology
Disease Management
Cell Biology
Original Articles
medicine.disease
biology.organism_classification
Polycystic Kidney
Autosomal Dominant
Hedgehog signaling pathway
female genital diseases and pregnancy complications
Clear cell renal cell carcinoma
Disease Models
Animal
Mutation
Molecular Medicine
Original Article
Metabolic Networks and Pathways
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
Popis: Autosomal‐dominant polycystic kidney disease (ADPKD) is characterized by uncontrolled renal cyst formation, and few treatment options are available. There are many parallels between ADPKD and clear‐cell renal cell carcinoma (ccRCC); however, few studies have addressed the mechanisms linking them. In this study, we aimed to investigate their convergences and divergences based on bioinformatics and explore the potential of compounds commonly used in cancer research to be repurposed for ADPKD. We analysed gene expression datasets of ADPKD and ccRCC to identify the common and disease‐specific differentially expressed genes (DEGs). We then mapped them to the Connectivity Map database to identify small molecular compounds with therapeutic potential. A total of 117 significant DEGs were identified, and enrichment analyses results revealed that they are mainly enriched in arachidonic acid metabolism, p53 signalling pathway and metabolic pathways. In addition, 127 ccRCC‐specific up‐regulated genes were identified as related to the survival of patients with cancer. We focused on the compound NS398 as it targeted DEGs and found that it inhibited the proliferation of Pkd1 −/− and 786‐0 cells. Furthermore, its administration curbed cystogenesis in Pkd2 zebrafish and early‐onset Pkd1‐deficient mouse models. In conclusion, NS398 is a potential therapeutic agent for ADPKD.
Databáze: OpenAIRE
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