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

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

doi:10.1007/s13258-024-01504-y

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저자정보: Luo Hongyan (Ningxia Medical University Affiliated People’s Hospital of Autonomous Region, People’s Republic of China) Yang Lirong (Ningxia Medical University Affiliated People’s Hospital of Autonomous Region, People’s Republic of China) Zhang Guoqing (Ningxia Medical University Affiliated People’s Hospital of Autonomous Region, People’s Republic of China) Bao Xi (Ningxia Medical University Affiliated People’s Hospital of Autonomous Region, People’s Republic of China) Ma Danna (Ningxia Medical University Affiliated People’s Hospital of Autonomous Region, People’s Republic of China) Li Bo (Ningxia Medical University Affiliated People’s Hospital of Autonomous Region, People’s Republic of China) Cao Li (Ningxia Medical University Affiliated People’s Hospital of Autonomous Region, People’s Republic of China) Cao Shilu (Ningxia Medical University Affiliated People’s Hospital of Autonomous Region, People’s Republic of China) Liu Shunyao (Ningxia Medical University Affiliated People’s Hospital of Autonomous Region, People’s Republic of China) Bao Li (Ningxia Medical University Affiliated People’s Hospital of Autonomous Region, People’s Republic of China) E Jing (Ningxia Medical University Affiliated People’s Hospital of Autonomous Region, People’s Republic of China) Zheng Yali (Ningxia Medical University Affiliated People’s Hospital of Autonomous Region, People’s Republic of China)

저널정보: 한국유전학회 Genes & Genomics Genes and Genomics Vol.46 No.5

발행연도: 2024.5

수록면: 621 - 635 (15page)

DOI: 10.1007/s13258-024-01504-y

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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.

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.

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