{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T23:18:34Z","timestamp":1784675914539,"version":"3.55.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:00:00Z","timestamp":1699401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of Hunan Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>We 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 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 <jats:italic>in vivo<\/jats:italic> 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 &amp;lt; 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 \u201cT cell receptor signaling pathway\u201d and \u201cpositive regulation of NF-\u03baB signaling pathway\u201d, were discovered to be associated not only with immune cell infiltration, but also with the expression levels of six IRGs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In summary, six IRGs were identified as key biomarkers for RIF, and exhibited a strong correlation with various T cells and with the NF-\u03baB signaling pathway. All these IRGs and their signaling pathways may evolve as valuable therapeutic targets for RIF in CKD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1207444","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T16:16:57Z","timestamp":1699546617000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Identification of the key immune-related genes and immune cell infiltration changes in renal interstitial fibrosis"],"prefix":"10.3389","volume":"14","author":[{"given":"Zhitao","family":"Dong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangzhi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiongfei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lizhe","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,11,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfw330","article-title":"The ascending rank of chronic kidney disease in the global burden of disease study","volume":"32","author":"Jager","year":"2017","journal-title":"Nephrol Dial Transpl"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2015.230","article-title":"A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010","volume":"88","author":"Mills","year":"2015","journal-title":"Kidney Int"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30045-3","article-title":"GBD Chronic Kidney Disease Collaboration. 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