GPX3 and GSTT1 as biomarkers related to oxidative stress during renal ischemia reperfusion injuries and their relationship with immune infiltration
BackgroundRenal ischemia reperfusion injuries (IRIs) are very common in clinical diagnoses and treatments, which are a common cause of impaired renal functions, worsening pathological damage, affecting disease progression and hindering recovery. Renal IRIs are an inflammatory disease mediated by the...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-03-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1136146/full |
| _version_ | 1797866065100800000 |
|---|---|
| author | Jun Pei Jun Pei Jun Pei Xiaomao Tian Xiaomao Tian Xiaomao Tian Chengjun Yu Chengjun Yu Chengjun Yu Jin Luo Jin Luo Jin Luo Jie Zhang Jie Zhang Jie Zhang Yi Hua Yi Hua Yi Hua Guanghui Wei Guanghui Wei Guanghui Wei |
| author_facet | Jun Pei Jun Pei Jun Pei Xiaomao Tian Xiaomao Tian Xiaomao Tian Chengjun Yu Chengjun Yu Chengjun Yu Jin Luo Jin Luo Jin Luo Jie Zhang Jie Zhang Jie Zhang Yi Hua Yi Hua Yi Hua Guanghui Wei Guanghui Wei Guanghui Wei |
| author_sort | Jun Pei |
| collection | DOAJ |
| description | BackgroundRenal ischemia reperfusion injuries (IRIs) are very common in clinical diagnoses and treatments, which are a common cause of impaired renal functions, worsening pathological damage, affecting disease progression and hindering recovery. Renal IRIs are an inflammatory disease mediated by the adaptive and innate immune system. There is a complex interaction between oxidative stress and immune cell infiltration. Therefore, we aimed to determine biomarkers associated with oxidative stress during renal IRIs and their relationship with immune cell infiltration.MethodA differential gene expression analysis was made based on the GSE148420 dataset from the NCBI Gene Expression Comprehensive Database (GEO) combined with 92 oxidative-stress (OS)-related genes identified in the Molecular Signatures Database. Then we identified differentially-expressed genes (DEOSGs) associated with oxidative stress, which were used for gene ontology (GO) and a Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. At the same time, we used PPI protein interaction networks and Lasso regression analysis to identify key genes, which were verified by the validation sets GSE58438 and GSE71647, as well as Western Blot detection on rat renal IRI models. At the same time, PAS staining, HE staining and immunohistochemistry were used to detect tissue damage and expression of markers related to oxidative stress during renal ischemia-reperfusion. Single-gene enrichment analysis (GSEA) was used to further clarify the underlying biological functions of key genes. Cibersort was used to analyze the immune cell infiltration during renal IRI and the correlation of key genes with immune cells. At the same time, we constructed a network of transcription-factor (TF)-Hub genes and miRNA-Hub genes. DGIDB was used to predict drugs and molecular compounds that might interact with the Hub genes.ResultsCompared with the control group, a total of 5456 differential genes (DEGs) were measured in the renal IRI group, 2486 of which were upregulated and 2970 were down-regulated. Among them, we found 30 DEGs (DEOSGs) associated with oxidative stress. The results of GO and KEGG enrichment analysis showed that these DEOSGs were mainly enriched in glutathione metabolism, the response to oxidative stress stimulation, the regulation of T cell activation and apoptosis signaling pathways. Through a protein interaction network (PPI) and a LASSO regression analysis, a total of two Hub genes were identified, namely GPX3 and GSTT1, which were validated through external validation sets and animal experiments. Through pathological methods, we found that the pathological damage of renal tissue and the expression of oxidative stress markers increased after renal ischemia-reperfusion. The results of GSEA showed that the Hub genes were related to oxidative stress pathways, apoptosis signaling pathways and immune-response-related signaling pathways. An immunoinfiltration correlation analysis showed that genes GPX3 and GSTT1 were significantly positively correlated with plasma cells and macrophage M0, while were negatively correlated with monocytes and macrophages M1 and M2. Using the Strust, Starbase and DGIDB database, we predicted that 81 transcription factors, 49 miRNAs and 13 drug or molecular compounds might interact with the Hub genes.ConclusionThrough a comprehensive analysis of gene expression, our findings may provide new potential biomarkers for the pathogenesis of renal IRIs and a reliable basis for its early diagnosis as well as treatment. |
| first_indexed | 2024-04-09T23:19:08Z |
| format | Article |
| id | doaj.art-f476d0929dc644b28310a6992d4e5e6e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-09T23:19:08Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f476d0929dc644b28310a6992d4e5e6e2023-03-22T05:25:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.11361461136146GPX3 and GSTT1 as biomarkers related to oxidative stress during renal ischemia reperfusion injuries and their relationship with immune infiltrationJun Pei0Jun Pei1Jun Pei2Xiaomao Tian3Xiaomao Tian4Xiaomao Tian5Chengjun Yu6Chengjun Yu7Chengjun Yu8Jin Luo9Jin Luo10Jin Luo11Jie Zhang12Jie Zhang13Jie Zhang14Yi Hua15Yi Hua16Yi Hua17Guanghui Wei18Guanghui Wei19Guanghui Wei20Department of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, ChinaDepartment of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, ChinaDepartment of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, ChinaDepartment of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, ChinaDepartment of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, ChinaDepartment of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, ChinaDepartment of Urology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaMinistry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Children Urogenital Development and Tissue Engineering, Chongqing, ChinaBackgroundRenal ischemia reperfusion injuries (IRIs) are very common in clinical diagnoses and treatments, which are a common cause of impaired renal functions, worsening pathological damage, affecting disease progression and hindering recovery. Renal IRIs are an inflammatory disease mediated by the adaptive and innate immune system. There is a complex interaction between oxidative stress and immune cell infiltration. Therefore, we aimed to determine biomarkers associated with oxidative stress during renal IRIs and their relationship with immune cell infiltration.MethodA differential gene expression analysis was made based on the GSE148420 dataset from the NCBI Gene Expression Comprehensive Database (GEO) combined with 92 oxidative-stress (OS)-related genes identified in the Molecular Signatures Database. Then we identified differentially-expressed genes (DEOSGs) associated with oxidative stress, which were used for gene ontology (GO) and a Kyoto Encyclopedia of Genomes (KEGG) enrichment analysis. At the same time, we used PPI protein interaction networks and Lasso regression analysis to identify key genes, which were verified by the validation sets GSE58438 and GSE71647, as well as Western Blot detection on rat renal IRI models. At the same time, PAS staining, HE staining and immunohistochemistry were used to detect tissue damage and expression of markers related to oxidative stress during renal ischemia-reperfusion. Single-gene enrichment analysis (GSEA) was used to further clarify the underlying biological functions of key genes. Cibersort was used to analyze the immune cell infiltration during renal IRI and the correlation of key genes with immune cells. At the same time, we constructed a network of transcription-factor (TF)-Hub genes and miRNA-Hub genes. DGIDB was used to predict drugs and molecular compounds that might interact with the Hub genes.ResultsCompared with the control group, a total of 5456 differential genes (DEGs) were measured in the renal IRI group, 2486 of which were upregulated and 2970 were down-regulated. Among them, we found 30 DEGs (DEOSGs) associated with oxidative stress. The results of GO and KEGG enrichment analysis showed that these DEOSGs were mainly enriched in glutathione metabolism, the response to oxidative stress stimulation, the regulation of T cell activation and apoptosis signaling pathways. Through a protein interaction network (PPI) and a LASSO regression analysis, a total of two Hub genes were identified, namely GPX3 and GSTT1, which were validated through external validation sets and animal experiments. Through pathological methods, we found that the pathological damage of renal tissue and the expression of oxidative stress markers increased after renal ischemia-reperfusion. The results of GSEA showed that the Hub genes were related to oxidative stress pathways, apoptosis signaling pathways and immune-response-related signaling pathways. An immunoinfiltration correlation analysis showed that genes GPX3 and GSTT1 were significantly positively correlated with plasma cells and macrophage M0, while were negatively correlated with monocytes and macrophages M1 and M2. Using the Strust, Starbase and DGIDB database, we predicted that 81 transcription factors, 49 miRNAs and 13 drug or molecular compounds might interact with the Hub genes.ConclusionThrough a comprehensive analysis of gene expression, our findings may provide new potential biomarkers for the pathogenesis of renal IRIs and a reliable basis for its early diagnosis as well as treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1136146/fulloxidative stressimmune infiltrationischemia-reperfusion injurykidneyGPX3 |
| spellingShingle | Jun Pei Jun Pei Jun Pei Xiaomao Tian Xiaomao Tian Xiaomao Tian Chengjun Yu Chengjun Yu Chengjun Yu Jin Luo Jin Luo Jin Luo Jie Zhang Jie Zhang Jie Zhang Yi Hua Yi Hua Yi Hua Guanghui Wei Guanghui Wei Guanghui Wei GPX3 and GSTT1 as biomarkers related to oxidative stress during renal ischemia reperfusion injuries and their relationship with immune infiltration Frontiers in Immunology oxidative stress immune infiltration ischemia-reperfusion injury kidney GPX3 |
| title | GPX3 and GSTT1 as biomarkers related to oxidative stress during renal ischemia reperfusion injuries and their relationship with immune infiltration |
| title_full | GPX3 and GSTT1 as biomarkers related to oxidative stress during renal ischemia reperfusion injuries and their relationship with immune infiltration |
| title_fullStr | GPX3 and GSTT1 as biomarkers related to oxidative stress during renal ischemia reperfusion injuries and their relationship with immune infiltration |
| title_full_unstemmed | GPX3 and GSTT1 as biomarkers related to oxidative stress during renal ischemia reperfusion injuries and their relationship with immune infiltration |
| title_short | GPX3 and GSTT1 as biomarkers related to oxidative stress during renal ischemia reperfusion injuries and their relationship with immune infiltration |
| title_sort | gpx3 and gstt1 as biomarkers related to oxidative stress during renal ischemia reperfusion injuries and their relationship with immune infiltration |
| topic | oxidative stress immune infiltration ischemia-reperfusion injury kidney GPX3 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1136146/full |
| work_keys_str_mv | AT junpei gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT junpei gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT junpei gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT xiaomaotian gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT xiaomaotian gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT xiaomaotian gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT chengjunyu gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT chengjunyu gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT chengjunyu gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT jinluo gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT jinluo gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT jinluo gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT jiezhang gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT jiezhang gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT jiezhang gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT yihua gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT yihua gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT yihua gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT guanghuiwei gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT guanghuiwei gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration AT guanghuiwei gpx3andgstt1asbiomarkersrelatedtooxidativestressduringrenalischemiareperfusioninjuriesandtheirrelationshipwithimmuneinfiltration |