Identification of the key immune-related genes and immune cell infiltration changes in renal interstitial fibrosis
BackgroundChronic kidney disease (CKD) is the third-leading cause of premature mortality worldwide. It is characterized by rapid deterioration due to renal interstitial fibrosis (RIF) via excessive inflammatory infiltration. The aim of this study was to discover key immune-related genes (IRGs) to pr...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1207444/full |
| _version_ | 1797632933786288128 |
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| author | Zhitao Dong Fangzhi Chen Shuang Peng Xiongfei Liu Xingyang Liu Lizhe Guo E. Wang E. Wang Xiang Chen Xiang Chen |
| author_facet | Zhitao Dong Fangzhi Chen Shuang Peng Xiongfei Liu Xingyang Liu Lizhe Guo E. Wang E. Wang Xiang Chen Xiang Chen |
| author_sort | Zhitao Dong |
| collection | DOAJ |
| description | BackgroundChronic kidney disease (CKD) is the third-leading cause of premature mortality worldwide. It is characterized by rapid deterioration due to renal interstitial fibrosis (RIF) via excessive inflammatory infiltration. The aim of this study was to discover key immune-related genes (IRGs) to provide valuable insights and therapeutic targets for RIF in CKD.Materials and methodsWe screened differentially expressed genes (DEGs) between RIF samples from CKD patients and healthy controls from a public database. Least absolute shrinkage and selection operator regression analysis and receiver operating characteristic curve analysis were applied to identify significant key biomarkers. The single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to analyze the infiltration of immune cells between the RIF and control samples. The correlation between biomarkers and immune cell composition was assessed.ResultsA total of 928 DEGs between CKD and control samples from six microarray datasets were found, 17 overlapping immune-correlated DEGs were identified by integration with the ImmPort database, and six IRGs were finally identified in the model: apolipoprotein H (APOH), epidermal growth factor (EGF), lactotransferrin (LTF), lysozyme (LYZ), phospholipid transfer protein (PLTP), and secretory leukocyte peptidase inhibitor (SLPI). Two additional datasets and in vivo experiments indicated that the expression levels of APOH and EGF in the fibrosis group were significantly lower than those in the control group, while the expression levels of LTF, LYZ, PLTP, and SLPI were higher (all P < 0.05). These IRGs also showed a significant correlation with renal function impairment. Moreover, four upregulated IRGs were positively associated with various T cell populations, which were enriched in RIF tissues, whereas two downregulated IRGs had opposite results. Several signaling pathways, such as the “T cell receptor signaling pathway” and “positive regulation of NF-κB signaling pathway”, were discovered to be associated not only with immune cell infiltration, but also with the expression levels of six IRGs.ConclusionIn summary, six IRGs were identified as key biomarkers for RIF, and exhibited a strong correlation with various T cells and with the NF-κB signaling pathway. All these IRGs and their signaling pathways may evolve as valuable therapeutic targets for RIF in CKD. |
| first_indexed | 2024-03-11T11:44:41Z |
| format | Article |
| id | doaj.art-88867c4cd1894cd59c6b99759d767b1e |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-11T11:44:41Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-88867c4cd1894cd59c6b99759d767b1e2023-11-09T16:16:42ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-11-011410.3389/fendo.2023.12074441207444Identification of the key immune-related genes and immune cell infiltration changes in renal interstitial fibrosisZhitao Dong0Fangzhi Chen1Shuang Peng2Xiongfei Liu3Xingyang Liu4Lizhe Guo5E. Wang6E. Wang7Xiang Chen8Xiang Chen9Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaNational Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Central South University, Changsha, Hunan, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaNational Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Central South University, Changsha, Hunan, ChinaBackgroundChronic kidney disease (CKD) is the third-leading cause of premature mortality worldwide. It is characterized by rapid deterioration due to renal interstitial fibrosis (RIF) via excessive inflammatory infiltration. The aim of this study was to discover key immune-related genes (IRGs) to provide valuable insights and therapeutic targets for RIF in CKD.Materials and methodsWe screened differentially expressed genes (DEGs) between RIF samples from CKD patients and healthy controls from a public database. Least absolute shrinkage and selection operator regression analysis and receiver operating characteristic curve analysis were applied to identify significant key biomarkers. The single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm was used to analyze the infiltration of immune cells between the RIF and control samples. The correlation between biomarkers and immune cell composition was assessed.ResultsA total of 928 DEGs between CKD and control samples from six microarray datasets were found, 17 overlapping immune-correlated DEGs were identified by integration with the ImmPort database, and six IRGs were finally identified in the model: apolipoprotein H (APOH), epidermal growth factor (EGF), lactotransferrin (LTF), lysozyme (LYZ), phospholipid transfer protein (PLTP), and secretory leukocyte peptidase inhibitor (SLPI). Two additional datasets and in vivo experiments indicated that the expression levels of APOH and EGF in the fibrosis group were significantly lower than those in the control group, while the expression levels of LTF, LYZ, PLTP, and SLPI were higher (all P < 0.05). These IRGs also showed a significant correlation with renal function impairment. Moreover, four upregulated IRGs were positively associated with various T cell populations, which were enriched in RIF tissues, whereas two downregulated IRGs had opposite results. Several signaling pathways, such as the “T cell receptor signaling pathway” and “positive regulation of NF-κB signaling pathway”, were discovered to be associated not only with immune cell infiltration, but also with the expression levels of six IRGs.ConclusionIn summary, six IRGs were identified as key biomarkers for RIF, and exhibited a strong correlation with various T cells and with the NF-κB signaling pathway. All these IRGs and their signaling pathways may evolve as valuable therapeutic targets for RIF in CKD.https://www.frontiersin.org/articles/10.3389/fendo.2023.1207444/fullchronic kidney diseaserenal interstitial fibrosisimmune cellsbiomarkerNF-κB signaling pathway |
| spellingShingle | Zhitao Dong Fangzhi Chen Shuang Peng Xiongfei Liu Xingyang Liu Lizhe Guo E. Wang E. Wang Xiang Chen Xiang Chen Identification of the key immune-related genes and immune cell infiltration changes in renal interstitial fibrosis Frontiers in Endocrinology chronic kidney disease renal interstitial fibrosis immune cells biomarker NF-κB signaling pathway |
| title | Identification of the key immune-related genes and immune cell infiltration changes in renal interstitial fibrosis |
| title_full | Identification of the key immune-related genes and immune cell infiltration changes in renal interstitial fibrosis |
| title_fullStr | Identification of the key immune-related genes and immune cell infiltration changes in renal interstitial fibrosis |
| title_full_unstemmed | Identification of the key immune-related genes and immune cell infiltration changes in renal interstitial fibrosis |
| title_short | Identification of the key immune-related genes and immune cell infiltration changes in renal interstitial fibrosis |
| title_sort | identification of the key immune related genes and immune cell infiltration changes in renal interstitial fibrosis |
| topic | chronic kidney disease renal interstitial fibrosis immune cells biomarker NF-κB signaling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1207444/full |
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