Revealing the molecular landscape of calcium oxalate renal calculi utilizing a tree shrew model: a transcriptomic analysis of the kidney.

IF 2 2区 医学 Q2 UROLOGY & NEPHROLOGY
Guang Wang, Ziye Huang, Yuyun Wu, Rui Xu, Jiongming Li
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引用次数: 0

Abstract

Our comprehensive genomic investigation employing tree shrew calcium oxalate stone models unveils intricate links between kidney stone formation and diverse physiological systems. We identify a constellation of genes whose expression patterns point to multifaceted interactions among cardiovascular health, renal fibrosis, and bone homeostasis in the pathogenesis of renal calculi. Key players include CHIT1, TNFRSF18, CLEC4E, RGS1, DCSTAMP, and SLC37A2, which emerge as pivotal actors in arteriosclerosis, renal fibrosis, and osteoclastogenesis respectively, showcasing the complexity of stone disease. The downregulation of ADRA1D, LVRN, and ABCG8 underscores roles in urodynamics, epithelial-mesenchymal transition, and vitamin D metabolism, linking these to nephrolithiasis. Comparative genomics across tree shrew, human (Randall's plaque), rat, and mouse identifies shared KEGG pathways including Calcium signaling, Actin cytoskeleton regulation, Neuroactive ligand-receptor interactions, Complement and coagulation cascades, TRP channel regulation by inflammatory mediators, p53 signaling, and Fc gamma R-mediated phagocytosis. These pathways underscore the interconnectedness of immune, inflammatory, and metabolic processes in stone development. Our findings suggest novel targets for future therapeutics and prevention strategies against nephrolithiasis, highlighting the need for a holistic view of the disease encompassing multiple pathogenic factors.

利用树鼩模型揭示草酸钙肾结石的分子图谱:肾脏转录组分析。
我们利用树鼩草酸钙结石模型进行的全面基因组研究揭示了肾结石形成与不同生理系统之间错综复杂的联系。我们发现了一组基因,它们的表达模式表明,在肾结石的发病机制中,心血管健康、肾脏纤维化和骨平衡之间存在着多方面的相互作用。其中的关键基因包括 CHIT1、TNFRSF18、CLEC4E、RGS1、DCSTAMP 和 SLC37A2,它们分别在动脉硬化、肾脏纤维化和破骨细胞生成过程中发挥关键作用,显示了结石病的复杂性。ADRA1D、LVRN和ABCG8的下调强调了它们在尿动力学、上皮-间质转化和维生素D代谢中的作用,并将这些作用与肾结石联系起来。树鼩、人类(兰德尔斑块)、大鼠和小鼠的比较基因组学发现了共享的 KEGG 通路,包括钙信号转导、肌动蛋白细胞骨架调节、神经活性配体-受体相互作用、补体和凝血级联、炎症介质对 TRP 通道的调节、p53 信号转导和 Fcγ R 介导的吞噬作用。这些途径强调了结石发育过程中免疫、炎症和代谢过程的相互关联性。我们的研究结果为未来肾结石的治疗和预防策略提出了新的靶点,强调了从整体上看待包括多种致病因素在内的肾结石的必要性。
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来源期刊
Urolithiasis
Urolithiasis UROLOGY & NEPHROLOGY-
CiteScore
4.50
自引率
6.50%
发文量
74
期刊介绍: Official Journal of the International Urolithiasis Society The journal aims to publish original articles in the fields of clinical and experimental investigation only within the sphere of urolithiasis and its related areas of research. The journal covers all aspects of urolithiasis research including the diagnosis, epidemiology, pathogenesis, genetics, clinical biochemistry, open and non-invasive surgical intervention, nephrological investigation, chemistry and prophylaxis of the disorder. The Editor welcomes contributions on topics of interest to urologists, nephrologists, radiologists, clinical biochemists, epidemiologists, nutritionists, basic scientists and nurses working in that field. Contributions may be submitted as full-length articles or as rapid communications in the form of Letters to the Editor. Articles should be original and should contain important new findings from carefully conducted studies designed to produce statistically significant data. Please note that we no longer publish articles classified as Case Reports. Editorials and review articles may be published by invitation from the Editorial Board. All submissions are peer-reviewed. Through an electronic system for the submission and review of manuscripts, the Editor and Associate Editors aim to make publication accessible as quickly as possible to a large number of readers throughout the world.
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