Hongyan Luo, Lirong Yang, Guoqing Zhang, Xi Bao, Danna Ma, Bo Li, Li Cao, Shilu Cao, Shunyao Liu, Li Bao, Jing E, Yali Zheng
{"title":"全转录组图谱揭示了TFP5治疗糖尿病肾病的lncRNA调控网络。","authors":"Hongyan Luo, Lirong Yang, Guoqing Zhang, Xi Bao, Danna Ma, Bo Li, Li Cao, Shilu Cao, Shunyao Liu, Li Bao, Jing E, Yali Zheng","doi":"10.1007/s13258-024-01504-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>TFP5 is a Cdk5 inhibitor peptide, which could restore insulin production. However, the role of TFP5 in diabetic nephropathy (DN) is still unclear.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Overall, the present study provides novel insights into molecular mechanisms of TFP5 treatment in DN.</p>","PeriodicalId":12675,"journal":{"name":"Genes & genomics","volume":" ","pages":"621-635"},"PeriodicalIF":1.6000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Whole transcriptome mapping reveals the lncRNA regulatory network of TFP5 treatment in diabetic nephropathy.\",\"authors\":\"Hongyan Luo, Lirong Yang, Guoqing Zhang, Xi Bao, Danna Ma, Bo Li, Li Cao, Shilu Cao, Shunyao Liu, Li Bao, Jing E, Yali Zheng\",\"doi\":\"10.1007/s13258-024-01504-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>TFP5 is a Cdk5 inhibitor peptide, which could restore insulin production. However, the role of TFP5 in diabetic nephropathy (DN) is still unclear.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>Overall, the present study provides novel insights into molecular mechanisms of TFP5 treatment in DN.</p>\",\"PeriodicalId\":12675,\"journal\":{\"name\":\"Genes & genomics\",\"volume\":\" \",\"pages\":\"621-635\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2024-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genes & genomics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s13258-024-01504-y\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/3/27 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genes & genomics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s13258-024-01504-y","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/27 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Whole transcriptome mapping reveals the lncRNA regulatory network of TFP5 treatment in diabetic nephropathy.
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.
期刊介绍：
Genes & Genomics is an official journal of the Korean Genetics Society (http://kgenetics.or.kr/). Although it is an official publication of the Genetics Society of Korea, membership of the Society is not required for contributors. It is a peer-reviewed international journal publishing print (ISSN 1976-9571) and online version (E-ISSN 2092-9293). It covers all disciplines of genetics and genomics from prokaryotes to eukaryotes from fundamental heredity to molecular aspects. The articles can be reviews, research articles, and short communications.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
