Huali Weng , Xingyu Pan , Jinpu Peng , Moudong Wu , Xiong Zhan , Guohua Zhu , Wei Wang , Nini An , Dan Wang , Jun Pei
{"title":"基于转录组学和动物实验评估 Sirtuins 家族在肾移植急性排斥反应中的诊断价值","authors":"Huali Weng , Xingyu Pan , Jinpu Peng , Moudong Wu , Xiong Zhan , Guohua Zhu , Wei Wang , Nini An , Dan Wang , Jun Pei","doi":"10.1016/j.trim.2024.102109","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>The Sirtuins (SIRT) family plays a key role in the diagnosis and treatment of many renal diseases, but no studies have been reported in acute rejection of kidney transplantation. The aim of this study was to explore the diagnostic value of SIRT family change characteristics in acute rejection of kidney transplantation.</p></div><div><h3>Methods</h3><p>We first explored the SIRT family expression profile in renal tissues using the HPA database; subsequently, we explored the potential biological functions and mechanistic changes during acute rejection of kidney transplantation by GSEA enrichment analysis. The Cibersort algorithm specifies the level of immune cell infiltration and explores the correlation between the SIRT family and immune cells using correlation analysis; Next, we constructed a diagnostic model using “Logistic regression analysis” and “Nomogram model”, and evaluated the diagnostic model using calibration curves and ROC curves, and the decision curve (DCA) was used to evaluate the clinical diagnostic value of SIRT family changes; Finally, we constructed a model of acute rejection of rat kidney transplantation, and assessed rat kidney function by detecting the levels of urea nitrogen and creatinine in serum. Meanwhile, the expression level of SIRT family in kidney tissues was initially verified by transcriptome sequencing and RT-PCR.</p></div><div><h3>Results</h3><p>We found that all seven SIRT family members were located and expressed in renal tissues. The results of enrichment analysis revealed that a large number of immune-related biological functions and pathways are activated during acute rejection of kidney transplantation, the difference was statistically significant (<em>p</em> < 0.05). The Cibersort algorithm revealed significant changes in the level of infiltration of 10 immune cells (<em>p</em> < 0.05), while correlation analysis revealed a strong link between the SIRT family and immune cells (p < 0.05). We constructed a diagnostic model for acute rejection using seven SIRT families, and the ROC curves(AUC = 0.71)and calibration curves proved their good diagnostic value, and the DCA curves also proved the role of SIRT families in clinical decision-making. Next, we again demonstrated the good diagnostic performance of the SIRT family in ABMR and TCMR, respectively(ROC curves:AUC = 0.64，AUC = 0.81). Finally, in a rat model of acute rejection of kidney transplantation, we found that renal function (BUN and creatinine) was significantly impaired in rats in the Allo group compared to rats in the Syn group (<em>P</em> < 0.05). Meanwhile, by transcriptome analysis and RT-PCR assay, we found that, except for SIRT1, the remaining SIRT family members were significantly changed in kidney tissues (<em>P</em> < 0.05).</p></div><div><h3>Conclusion</h3><p>The SIRT family has significant changes during acute rejection in kidney transplantation, and the SIRT family may be able to serve as a potential therapeutic target for alleviating acute rejection in kidney transplantation.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"86 ","pages":"Article 102109"},"PeriodicalIF":1.6000,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Diagnostic value of the Sirtuins family in acute rejection of kidney transplantation assessed on the basis of transcriptomics and animal experiments\",\"authors\":\"Huali Weng , Xingyu Pan , Jinpu Peng , Moudong Wu , Xiong Zhan , Guohua Zhu , Wei Wang , Nini An , Dan Wang , Jun Pei\",\"doi\":\"10.1016/j.trim.2024.102109\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>The Sirtuins (SIRT) family plays a key role in the diagnosis and treatment of many renal diseases, but no studies have been reported in acute rejection of kidney transplantation. The aim of this study was to explore the diagnostic value of SIRT family change characteristics in acute rejection of kidney transplantation.</p></div><div><h3>Methods</h3><p>We first explored the SIRT family expression profile in renal tissues using the HPA database; subsequently, we explored the potential biological functions and mechanistic changes during acute rejection of kidney transplantation by GSEA enrichment analysis. The Cibersort algorithm specifies the level of immune cell infiltration and explores the correlation between the SIRT family and immune cells using correlation analysis; Next, we constructed a diagnostic model using “Logistic regression analysis” and “Nomogram model”, and evaluated the diagnostic model using calibration curves and ROC curves, and the decision curve (DCA) was used to evaluate the clinical diagnostic value of SIRT family changes; Finally, we constructed a model of acute rejection of rat kidney transplantation, and assessed rat kidney function by detecting the levels of urea nitrogen and creatinine in serum. Meanwhile, the expression level of SIRT family in kidney tissues was initially verified by transcriptome sequencing and RT-PCR.</p></div><div><h3>Results</h3><p>We found that all seven SIRT family members were located and expressed in renal tissues. The results of enrichment analysis revealed that a large number of immune-related biological functions and pathways are activated during acute rejection of kidney transplantation, the difference was statistically significant (<em>p</em> < 0.05). The Cibersort algorithm revealed significant changes in the level of infiltration of 10 immune cells (<em>p</em> < 0.05), while correlation analysis revealed a strong link between the SIRT family and immune cells (p < 0.05). We constructed a diagnostic model for acute rejection using seven SIRT families, and the ROC curves(AUC = 0.71)and calibration curves proved their good diagnostic value, and the DCA curves also proved the role of SIRT families in clinical decision-making. Next, we again demonstrated the good diagnostic performance of the SIRT family in ABMR and TCMR, respectively(ROC curves:AUC = 0.64，AUC = 0.81). Finally, in a rat model of acute rejection of kidney transplantation, we found that renal function (BUN and creatinine) was significantly impaired in rats in the Allo group compared to rats in the Syn group (<em>P</em> < 0.05). 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Diagnostic value of the Sirtuins family in acute rejection of kidney transplantation assessed on the basis of transcriptomics and animal experiments
Background
The Sirtuins (SIRT) family plays a key role in the diagnosis and treatment of many renal diseases, but no studies have been reported in acute rejection of kidney transplantation. The aim of this study was to explore the diagnostic value of SIRT family change characteristics in acute rejection of kidney transplantation.
Methods
We first explored the SIRT family expression profile in renal tissues using the HPA database; subsequently, we explored the potential biological functions and mechanistic changes during acute rejection of kidney transplantation by GSEA enrichment analysis. The Cibersort algorithm specifies the level of immune cell infiltration and explores the correlation between the SIRT family and immune cells using correlation analysis; Next, we constructed a diagnostic model using “Logistic regression analysis” and “Nomogram model”, and evaluated the diagnostic model using calibration curves and ROC curves, and the decision curve (DCA) was used to evaluate the clinical diagnostic value of SIRT family changes; Finally, we constructed a model of acute rejection of rat kidney transplantation, and assessed rat kidney function by detecting the levels of urea nitrogen and creatinine in serum. Meanwhile, the expression level of SIRT family in kidney tissues was initially verified by transcriptome sequencing and RT-PCR.
Results
We found that all seven SIRT family members were located and expressed in renal tissues. The results of enrichment analysis revealed that a large number of immune-related biological functions and pathways are activated during acute rejection of kidney transplantation, the difference was statistically significant (p < 0.05). The Cibersort algorithm revealed significant changes in the level of infiltration of 10 immune cells (p < 0.05), while correlation analysis revealed a strong link between the SIRT family and immune cells (p < 0.05). We constructed a diagnostic model for acute rejection using seven SIRT families, and the ROC curves(AUC = 0.71)and calibration curves proved their good diagnostic value, and the DCA curves also proved the role of SIRT families in clinical decision-making. Next, we again demonstrated the good diagnostic performance of the SIRT family in ABMR and TCMR, respectively(ROC curves:AUC = 0.64，AUC = 0.81). Finally, in a rat model of acute rejection of kidney transplantation, we found that renal function (BUN and creatinine) was significantly impaired in rats in the Allo group compared to rats in the Syn group (P < 0.05). Meanwhile, by transcriptome analysis and RT-PCR assay, we found that, except for SIRT1, the remaining SIRT family members were significantly changed in kidney tissues (P < 0.05).
Conclusion
The SIRT family has significant changes during acute rejection in kidney transplantation, and the SIRT family may be able to serve as a potential therapeutic target for alleviating acute rejection in kidney transplantation.
期刊介绍：
Transplant Immunology will publish up-to-date information on all aspects of the broad field it encompasses. The journal will be directed at (basic) scientists, tissue typers, transplant physicians and surgeons, and research and data on all immunological aspects of organ-, tissue- and (haematopoietic) stem cell transplantation are of potential interest to the readers of Transplant Immunology. Original papers, Review articles and Hypotheses will be considered for publication and submitted manuscripts will be rapidly peer-reviewed and published. They will be judged on the basis of scientific merit, originality, timeliness and quality.
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