Dahl SS大鼠肾小球转录组学变化对高盐挑战的反应。

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-01-01 Epub Date: 2023-11-13 DOI:10.1152/physiolgenomics.00075.2023
Marharyta Semenikhina, Daria V Lysikova, Denisha R Spires, Mark Domondon, Krisztian Stadler, Oleg Palygin, Daria V Ilatovskaya
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引用次数: 0

摘要

盐敏感性影响了很大一部分人群,是慢性肾脏疾病发展的重要因素。其中一个重要的早期预测因素是蛋白尿,它反映了肾滤过屏障-肾小球的恶化。尽管进行了大量的研究工作,但在促进和/或持续盐性肾小球损伤的分子机制和信号网络方面的知识仍然存在空白。为了解决这一差距,我们使用8周龄雄性达尔盐敏感(SS)大鼠,喂食正常(0.4% NaCl, NS)或高盐饮食(4% NaCl, HS) 3周。在方案结束时,通过差筛获得的肾小球的纯部分用于下一代RNA测序和全面的半自动转录组数据分析,发现149个差异表达基因(分别为107和42下调和上调)。此外,预测基因相关网络和计算生物信息学分析的结合揭示了受HS饮食挑战影响的途径,包括肾脏代谢、线粒体功能、凋亡信号和纤维化、细胞周期、炎症和免疫反应、生物钟、细胞骨架组织、GPCR信号和钙运输。总之,我们在此报告了盐诱导应激下影响肾小球的新的转录组相互作用和相应的预测途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Transcriptomic changes in glomeruli in response to a high salt challenge in the Dahl SS rat.

Salt sensitivity impacts a significant portion of the population and is an important contributor to the development of chronic kidney disease. One of the significant early predictors of salt-induced damage is albuminuria, which reflects the deterioration of the renal filtration barrier: the glomerulus. Despite significant research efforts, there is still a gap in knowledge regarding the molecular mechanisms and signaling networks contributing to instigating and/or perpetuating salt-induced glomerular injury. To address this gap, we used 8-wk-old male Dahl salt-sensitive rats fed a normal-salt diet (0.4% NaCl) or challenged with a high-salt diet (4% NaCl) for 3 wk. At the end of the protocol, a pure fraction of renal glomeruli obtained by differential sieving was used for next-generation RNA sequencing and comprehensive semi-automatic transcriptomic data analyses, which revealed 149 differentially expressed genes (107 and 42 genes were downregulated and upregulated, respectively). Furthermore, a combination of predictive gene correlation networks and computational bioinformatic analyses revealed pathways impacted by a high salt dietary challenge, including renal metabolism, mitochondrial function, apoptotic signaling and fibrosis, cell cycle, inflammatory and immune responses, circadian clock, cytoskeletal organization, G protein-coupled receptor signaling, and calcium transport. In conclusion, we report here novel transcriptomic interactions and corresponding predicted pathways affecting glomeruli under salt-induced stress.NEW & NOTEWORTHY Our study demonstrated novel pathways affecting glomeruli under stress induced by dietary salt. Predictive gene correlation networks and bioinformatic semi-automatic analysis revealed changes in the pathways relevant to mitochondrial function, inflammatory, apoptotic/fibrotic processes, and cell calcium transport.

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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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