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基于纳米孔的全长转录组测序,用于了解糖尿病肾病快速和缓慢进展的潜在分子机制。

Nanopore-based full-length transcriptome sequencing for understanding the underlying molecular mechanisms of rapid and slow progression of diabetes nephropathy.

机构信息

Department of Nephrology, People's Hospital of Ningxia Hui Autonomous Region, People's Hospital of Ningxia Hui Autonomous Region, No.157, West 5th Road, Yinchuan, 750002, China.

Department of clinical medicine, Xi'an Jiaotong University, Xi'an, China.

出版信息

BMC Med Genomics. 2024 Oct 8;17(1):246. doi: 10.1186/s12920-024-02006-2.

Abstract

BACKGROUND

Diabetic nephropathy (DN) has been a major factor in the outbreak of end-stage renal disease for decades. As the underlying mechanisms of DN development remains unclear, there is no ideal methods for the diagnosis and therapy.

OBJECTIVE

We aimed to explore the key genes and pathways that affect the rate progression of DN.

METHODS

Nanopore-based full-length transcriptome sequencing was performed with serum samples from DN patients with slow progression (DNSP, n = 5) and rapid progression (DNRP, n = 6).

RESULTS

Here, transcriptome proclaimed 22,682 novel transcripts and obtained 45,808 simple sequence repeats, 1,815 transcription factors, 5,993 complete open reading frames, and 1,050 novel lncRNA from the novel transcripts. Moreover, a total of 341 differentially expressed transcripts (DETs) and 456 differentially expressed genes (DEGs) between the DNSP and DNRP groups were identified. Functional analyses showed that DETs mainly involved in ferroptosis-related pathways such as oxidative phosphorylation, iron ion binding, and mitophagy. Moreover, Functional analyses revealed that DEGs mainly involved in oxidative phosphorylation, lipid metabolism, ferroptosis, autophagy/mitophagy, apoptosis/necroptosis pathway.

CONCLUSION

Collectively, our study provided a full-length transcriptome data source for the future DN research, and facilitate a deeper understanding of the molecular mechanisms underlying the differences in fast and slow progression of DN.

摘要

背景

几十年来,糖尿病肾病 (DN) 一直是终末期肾病爆发的主要因素。由于 DN 发展的潜在机制尚不清楚,因此目前还没有理想的诊断和治疗方法。

目的

我们旨在探讨影响 DN 进展速度的关键基因和途径。

方法

对进展缓慢的 DN 患者 (DNSP,n = 5) 和进展迅速的 DN 患者 (DNRP,n = 6) 的血清样本进行基于纳米孔的全长转录组测序。

结果

本研究共获得了 22682 个新的转录本,获得了 45808 个简单重复序列、1815 个转录因子、5993 个完整的开放阅读框和 1050 个新的 lncRNA。此外,在 DNSP 和 DNRP 两组之间共鉴定出 341 个差异表达的转录本 (DETs) 和 456 个差异表达基因 (DEGs)。功能分析表明,DETs 主要参与铁死亡相关途径,如氧化磷酸化、铁离子结合和线粒体自噬。此外,功能分析表明,DEGs 主要参与氧化磷酸化、脂质代谢、铁死亡、自噬/线粒体自噬、细胞凋亡/坏死途径。

结论

总之,我们的研究为未来的 DN 研究提供了一个全长转录组数据集,并有助于更深入地了解 DN 快速和缓慢进展的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c6f/11463056/5d882a224cee/12920_2024_2006_Fig1_HTML.jpg

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