{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:54:47Z","timestamp":1753890887389,"version":"3.41.2"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["No.2019J01184, No.2021J05056"],"award-info":[{"award-number":["No.2019J01184, No.2021J05056"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Lupus nephritis (LN) is a major risk factor of morbidity and mortality. Glomerular injury is associated with different pathogeneses and clinical presentations in LN patients. However, the molecular mechanisms involved are not well understood. This study aimed to explore the molecular characteristics and mechanisms of this disease using bioinformatics analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To characterize glomeruli in LN, microarray datasets GSE113342 and GSE32591 were downloaded from the Gene Expression Omnibus database and analyzed to determine the differentially expressed genes (DEGs) between LN glomeruli and normal glomeruli. Functional enrichment analyses and protein\u2013protein interaction network analyses were then performed. Module analysis was performed using the Search Tool for the Retrieval of Interacting Genes\/Proteins and Cytoscape software. Immunofluorescence staining was performed to identify the glomerular expression of S100A8 in various International Society of Nephrology\/Renal Pathology Society (ISN\/RPS) class LN patients. The image of each glomerulus was acquired using a digital imaging system, and the green fluorescence intensity was quantified using Image-Pro Plus software.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 13 DEGs, consisting of 12 downregulated genes and one upregulated gene (S100A8), were identified in the microarray datasets. The functions and pathways associated with the DEGs mainly include inflammatory response, innate immune response, neutrophil chemotaxis, leukocyte migration, cell adhesion, cell\u2013cell signaling, and infection. We also found that monocytes and activated natural killer cells were upregulated in both GSE113342 and GSE32591. Glomerular S100A8 staining was significantly enhanced compared to that in the controls, especially in class IV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The DEGs identified in the present study help us understand the underlying molecular mechanisms of LN. Our results show that glomerular S100A8 expression varies in different pathological types; however, further research is required to confirm the role of S100A8 in LN.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.843576","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T08:36:37Z","timestamp":1651048597000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Glomerular Expression of S100A8 in Lupus Nephritis: An Integrated Bioinformatics Analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Wei","family":"Qijiao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Zhihan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panashe","family":"Makota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Qing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gao","family":"Fei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang","family":"Zhihong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.05780616","article-title":"Update on Lupus Nephritis","volume":"12","author":"Almaani","year":"2017","journal-title":"Clin J Am Soc Nephrol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ket491","article-title":"Podocyte Involvement in Lupus Nephritis Based on the 2003 ISN\/RPS System: A Large Cohort Study From a Single Center","volume":"53","author":"Wang","year":"2014","journal-title":"Rheumatology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.22438.1","article-title":"A Review of Advances in the Understanding of Lupus Nephritis Pathogenesis as a Basis for Emerging Therapies","volume":"9","author":"Yung","year":"2020","journal-title":"F1000Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01298","article-title":"S100A8\/A9 in Inflammation","volume":"9","author":"Wang","year":"2018","journal-title":"Front Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2016.07.015","article-title":"S100A8\/A9: From Basic Science to Clinical Application","volume":"167","author":"Pruenster","year":"2016","journal-title":"Pharmacol Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.03.088","article-title":"Neutrophil-Derived Exosome From Systemic Sclerosis Inhibits the Proliferation and Migration of Endothelial Cells","volume":"526","author":"Liya","year":"2020","journal-title":"Biochem Biophys Res Commun"},{"key":"B7","doi-asserted-by":"publisher","first-page":"108375","DOI":"10.1016\/j.clim.2020.108375","article-title":"Differential Analysis of Serum and Urine S100 Proteins in Juvenile-Onset Systemic Lupus Erythematosus (jSLE)","volume":"214","author":"Donohue","year":"2020","journal-title":"Clin Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1186\/s13075-017-1444-4","article-title":"Urine S100 Proteins as Potential Biomarkers of Lupus Nephritis Activity","volume":"19","author":"Turnier","year":"2017","journal-title":"Arthritis Res Ther"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkl887","article-title":"NCBI GEO: Mining Tens of Millions of Expression Profiles\u2013Database and Tools Update","volume":"35","author":"Barrett","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"B10","unstructured":""},{"key":"B11","unstructured":""},{"key":"B12","doi-asserted-by":"publisher","first-page":"P3","DOI":"10.1186\/gb-2003-4-5-p3","article-title":"DAVID: Database for Annotation, Visualization, and Integrated Discovery","volume":"4","author":"Dennis","year":"2003","journal-title":"Genome Biol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/nar\/27.1.29","article-title":"KEGG: Kyoto Encyclopedia of Genes and Genomes","volume":"27","author":"Ogata","year":"1999","journal-title":"Nucleic Acids Res"},{"key":"B14","unstructured":""},{"key":"B15","unstructured":""},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1159\/000496006","article-title":"Overproduction of Mitochondrial Fission Proteins in Membranous Nephropathy in Children","volume":"43","author":"QiJiao","year":"2018","journal-title":"Kidney Blood Press Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"37","DOI":"10.3969\/cndt.j.issn.1006\u2014298X.2017.01.007","article-title":"Mitochondrial Fission Proteins Are Involved in Proteinuria in Adriamycin-Induced Rat Nephropathy","volume":"26","author":"QiJiao","year":"2017","journal-title":"J Nephrol Dialy Transplant"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201646387","article-title":"Mapping Urinary Chemokines in Human Lupus Nephritis: Potentially Redundant Pathways Recruit CD4+ and CD8+ T Cells and Macrophages","volume":"47","author":"Klocke","year":"2017","journal-title":"Eur J Immunol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"207190","DOI":"10.1155\/2012\/207190","article-title":"The Role of Hyaluronan and CD44 in the Pathogenesis of Lupus Nephritis","volume":"2012","author":"Yung","year":"2012","journal-title":"Autoimmune Dis"},{"key":"B20","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1159\/000496006","article-title":"Effect of Ligustrazine Nanoparticles on Th1\/Th2 Balance by TLR4\/MyD88\/NF-\u03bab Pathway in Rats With Postoperative Peritoneal Adhesion","volume":"21","author":"Yang","year":"2021","journal-title":"BMC Surg"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1580512","article-title":"Podocytes and Autophagy: A Potential Therapeutic Target in Lupus Nephritis","volume":"15","author":"Zhou","year":"2019","journal-title":"Autophagy"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-014-3156-2","article-title":"Association Between the Functional ITGAM Rs1143679 G\/A Polymorphism and Systemic Lupus Erythematosus\/Lupus Nephritis or Rheumatoid Arthritis: An Update Meta-Analysis","volume":"35","author":"Lee","year":"2015","journal-title":"Rheumatol Int"},{"key":"B23","doi-asserted-by":"publisher","first-page":"155640","DOI":"10.1016\/j.cyto.2021.155640","article-title":"A Review on the Role of Chemokines in the Pathogenesis of Systemic Lupus Erythematosus","volume":"146","author":"Ghafouri-Fard","year":"2021","journal-title":"Cytokine"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218373","article-title":"Toll-Like Receptors Revisited; a Possible Role for TLR1 in Lupus Nephritis","volume":"80","author":"Yavuz","year":"2020","journal-title":"Ann Rheum Dis"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.717234","article-title":"Prioritization of Diagnostic and Prognostic Biomarkers for Lupus Nephritis Based on Integrated Bioinformatics Analyses","volume":"9","author":"Chen","year":"2021","journal-title":"Front Bioeng Biotechnol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1186\/s13075-021-02605-9","article-title":"Microarray-Based Analysis of Renal Complement Components Reveals a Therapeutic Target for Lupus Nephritis","volume":"23","author":"Liu","year":"2021","journal-title":"Arthritis Res Ther"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2174\/1386207323666200416151836","article-title":"A Comparative Study on the Incidence, Aggravation, and Remission of Lupus Nephritis Based on iTRAQ Technology","volume":"23","author":"Liao","year":"2020","journal-title":"Comb Chem High Throughput Screen"},{"key":"B28","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s12865-019-0316-x","article-title":"Immune Cell Infiltration Characteristics and Related Core Genes in Lupus Nephritis: Results From Bioinformatic Analysis","volume":"20","author":"Cao","year":"2019","journal-title":"BMC Immunol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1097\/BOR.0000000000000777","article-title":"Cellular Aspects of the Pathogenesis of Lupus Nephritis","volume":"33","author":"Chang","year":"2021","journal-title":"Curr Opin Rheumatol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126564","article-title":"Novel Autoantigens Associated With Lupus Nephritis","volume":"10","author":"Onishi","year":"2015","journal-title":"PloS One"},{"key":"B31","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1191\/096120398678920712","article-title":"Cellular Interactions in the Pathogenesis of Lupus Nephritis: The Role of T Cells and Macrophages in the Amplification of the Inflammatory Process in the Kidney","volume":"7","author":"Kuroiwa","year":"1998","journal-title":"Lupus"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay1620","article-title":"Kidney Tissue Hypoxia Dictates T Cell-Mediated Injury in Murine Lupus Nephritis","volume":"12","author":"Chen","year":"2020","journal-title":"Sci Transl Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaa053","article-title":"Immunological Characteristics and Possible Pathogenic Role of Urinary CD11c+ Macrophages in Lupus Nephritis","volume":"59","author":"Kim","year":"2020","journal-title":"Rheumatol (Oxford)"},{"key":"B34","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1189\/jlb.0306170","article-title":"S100 Proteins Expressed in Phagocytes: A Novel Group of Damage-Associated Molecular Pattern Molecules","volume":"81","author":"Foell","year":"2007","journal-title":"J Leukoc Biol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1189\/jlb.0203076","article-title":"Expression of MRP8 and MRP14 by Macrophages Is a Marker for Severe Forms of Glomerulonephritis","volume":"75","author":"Frosch","year":"2004","journal-title":"J Leukoc Biol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/ijms160614276","article-title":"Biomarkers for Refractory Lupus Nephritis: A Microarray Study of Kidney Tissue","volume":"16","author":"Benjachat","year":"2015","journal-title":"Int J Mol Sci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2020-001257","article-title":"Urine and Serum S100A8\/A9 and S100A12 Associate With Active Lupus Nephritis and may Predict Response to Rituximab Treatment","volume":"6","author":"Davies","year":"2020","journal-title":"RMD Open"},{"key":"B38","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1177\/0961203315598015","article-title":"Elevated Expressions of Myeloid-Related Proteins-8 and -14 are Danger Biomarkers for Lupus Nephritis","volume":"25","author":"Tantivitayakul","year":"2016","journal-title":"Lupus"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.039262","article-title":"S100a8\/a9 Signaling Causes Mitochondrial Dysfunction and Cardiomyocyte Death in Response to Ischemic\/Reperfusion Injury","volume":"140","author":"Li","year":"2019","journal-title":"Circulation"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.843576\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T08:36:54Z","timestamp":1651048614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.843576\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,27]]},"references-count":39,"alternative-id":["10.3389\/fimmu.2022.843576"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.843576","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2022,4,27]]},"article-number":"843576"}}