Whole transcriptome mapping reveals the lncRNA regulatory network of TFP5 treatment in diabetic nephropathy.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-05-01 Epub Date: 2024-03-27 DOI:10.1007/s13258-024-01504-y

Hongyan Luo, Lirong Yang, Guoqing Zhang, Xi Bao, Danna Ma, Bo Li, Li Cao, Shilu Cao, Shunyao Liu, Li Bao, Jing E, Yali Zheng

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Abstract

Background: TFP5 is a Cdk5 inhibitor peptide, which could restore insulin production. However, the role of TFP5 in diabetic nephropathy (DN) is still unclear.

Objective: This study aims to characterize the transcriptome profiles of mRNA and lncRNA in TFP5-treated DN mice to mine key lncRNAs associated with TFP5 efficacy.

Methods: We evaluated the role of TFP5 in DN pathology and performed RNA sequencing in C57BL/6J control mice, C57BL/6J db/db model mice, and TFP5 treatment C57BL/6J db/db model mice. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were analyzed. WGCNA was used to screen hub-gene of TFP5 in treatment of DN.

Results: Our results showed that TFP5 therapy ameliorated renal tubular injury in DN mice. In addition, compared with the control group, the expression profile of lncRNAs in the model group was significantly disordered, while TFP5 alleviated the abnormal expression of lncRNAs. A total of 67 DElncRNAs shared among the three groups, 39 DElncRNAs showed a trend of increasing in the DN group and decreasing after TFP treatment, while the remaining 28 showed the opposite trend. DElncRNAs were enriched in glycosphingolipid biosynthesis signaling pathways, NF-κB signaling pathways, and complement activation signaling pathways. There were 1028 up-regulated and 1117 down-regulated DEmRNAs in the model group compared to control group, and 123 up-regulated and 153 down-regulated DEmRNAs in the TFP5 group compared to the model group. The DEmRNAs were involved in PPAR and MAPK signaling pathway. We confirmed that MSTRG.28304.1 is a key DElncRNA for TFP5 treatment of DN. TFP5 ameliorated DN maybe by inhibiting MSTRG.28304.1 through regulating the insulin resistance and PPAR signaling pathway. The qRT-PCR results confirmed the reliability of the sequencing data through verifying the expression of ENSMUST00000211209, MSTRG.31814.5, MSTRG.28304.1, and MSTRG.45642.14.

Conclusion: Overall, the present study provides novel insights into molecular mechanisms of TFP5 treatment in DN.

Abstract Image

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全转录组图谱揭示了TFP5治疗糖尿病肾病的lncRNA调控网络。

背景TFP5是一种Cdk5抑制肽，可恢复胰岛素分泌。然而，TFP5 在糖尿病肾病（DN）中的作用仍不清楚：本研究旨在描述经 TFP5 治疗的 DN 小鼠 mRNA 和 lncRNA 的转录组特征，以挖掘与 TFP5 疗效相关的关键 lncRNA：我们评估了TFP5在DN病理学中的作用，并对C57BL/6J对照组小鼠、C57BL/6J db/db模型小鼠和TFP5治疗的C57BL/6J db/db模型小鼠进行了RNA测序。对差异表达的lncRNAs（DElncRNAs）和mRNAs（DEmRNAs）进行了分析。用WGCNA筛选TFP5治疗DN的枢纽基因：结果表明，TFP5 治疗可改善 DN 小鼠的肾小管损伤。此外，与对照组相比，模型组 lncRNAs 的表达谱明显紊乱，而 TFP5 则缓解了 lncRNAs 的异常表达。三组共有67个DElncRNAs，其中39个DElncRNAs在DN组呈上升趋势，在TFP处理后呈下降趋势，其余28个呈相反趋势。DElncRNA富集于糖磷脂生物合成信号通路、NF-κB信号通路和补体激活信号通路。与对照组相比，模型组有1028个DEmRNA上调，1117个DEmRNA下调；与模型组相比，TFP5组有123个DEmRNA上调，153个DEmRNA下调。这些 DEmRNA 参与了 PPAR 和 MAPK 信号通路。我们证实MSTRG.28304.1是TFP5治疗DN的关键DElncRNA。TFP5可通过调节胰岛素抵抗和PPAR信号通路抑制MSTRG.28304.1，从而改善DN。qRT-PCR结果通过验证ENSMUST00000211209、MSTRG.31814.5、MSTRG.28304.1和MSTRG.45642.14的表达，证实了测序数据的可靠性：总之，本研究为 TFP5 治疗 DN 的分子机制提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.