{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:52:53Z","timestamp":1786121573342,"version":"build-2736575974"},"reference-count":73,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Immunoglobulin A nephropathy (IgAN) is a major cause of chronic kidney disease and kidney failure. Currently, arginine metabolism (AM)-related genes (AMRGs) have been reported to play direct or indirect roles in various kidney-related diseases. This study aimed to identify AM-associated key genes in IgAN, potentially paving the way for targeted therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The data pertaining to IgAN and AMRGs were procured from public databases and literature, respectively. Candidate genes were obtained by integrating differentially expressed genes (DEGs) with AMRGs, and the genes were experimentally verified using qPCR. The identification of key genes was facilitated by machine learning algorithms and gene expression analyses. Of particular significance was the use of the nomogram to evaluate the diagnostic efficacy of these key genes. Functional enrichment, immune infiltration, drug prediction, and molecular docking analyses were performed. Single-cell analysis was employed to ascertain cell types, with the identification of key cells facilitated by key genes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ARG1 and ARG2 were identified as key genes, and the expression of these 2 genes was found to be downregulated in IgAN samples. The nomogram developed utilizing these key genes demonstrated a satisfactory capacity for differentiating among various sample types. The key genes were found to be enriched in several signaling pathways, including PIP3 signaling in B lymphocytes and BCR signaling pathway. Furthermore, most of the differential immune cells showed significant negative correlations with key genes. Effector memory CD8+ T cells exhibited extremely significant negative correlations with both ARG1 and ARG2 (correlation coefficient (r) &amp;lt; -0.70, P &amp;lt; 0.001). Riluzole exhibited strong binding affinity for key genes and formed stable complexes. Finally, monocytes were considered key cells and played a critical role in IgAN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study suggests that ARG1 and ARG2 may be key genes and potential mechanistic indicators of IgAN associated with AM, but it needs to be further verified in non-invasive samples and larger independent cohorts. Additionally, monocytes were recognized as key cells in the progression of IgAN, providing valuable insights to support the development of targeted therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1888069","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T05:29:33Z","timestamp":1786080573000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of key genes related to arginine metabolism in immunoglobulin A nephropathy through the combination of scRNA-seq and bulk RNA-seq data"],"prefix":"10.3389","volume":"17","author":[{"given":"Hong","family":"Xia","sequence":"first","affiliation":[{"name":"Zhejiang Chinese Medical University","place":["Hangzhou, China"]},{"name":"Nephrology Department, The First Affiliated Hospital of Zhejiang Chinese Medical University","place":["Hangzhou, 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