{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T21:37:25Z","timestamp":1773956245164,"version":"3.50.1"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangxi Clinical Research Center for Pediatric disease","award":["AD22035219"],"award-info":[{"award-number":["AD22035219"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Background<\/jats:title>\n Lupus nephritis (LN), a prevalent and serious manifestation of systemic lupus erythematosus, exhibits particularly high incidence in children, yet its pathogenesis remains incompletely elucidated. This study aimed to investigate differentially expressed genes in LN and elucidate their regulatory mechanisms.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Bioinformatics analysis was conducted on the publicly available glomerular gene expression dataset GSE32591 from the Gene Expression Omnibus to identify hub genes. Based on this screening, Guanylate-binding protein 2 (\n GBP2<\/jats:italic>\n ) was selected for further investigation. In vivo, GBP2 expression was assessed in renal tissues from pediatric LN patients by immunohistochemistry. In a murine LN model, the expression levels of GBP2 and key pyroptosis-associated markers were evaluated using immunohistochemistry, RT-qPCR, and western blotting. In vitro, a podocyte pyroptosis model was induced by lipopolysaccharide and adenosine triphosphate treatment. Functional experiments involving\n Gbp2<\/jats:italic>\n knockdown and overexpression, followed by a rescue experiment where absent in melanoma 2 (\n Aim2<\/jats:italic>\n ) was overexpressed in\n Gbp2<\/jats:italic>\n -knockdown cells, were performed to elucidate its role and underlying mechanisms in regulating pyroptosis.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Bioinformatics analysis identified\n OAS1<\/jats:italic>\n ,\n OAS2<\/jats:italic>\n ,\n IRF7<\/jats:italic>\n ,\n GBP2<\/jats:italic>\n , and\n GBP1<\/jats:italic>\n as hub genes. An upregulation of GBP2 and gasdermin D (GSDMD) was observed in the glomeruli of children with LN, showing a strong correlation with 24-hour urinary protein excretion. Renal tissues from LN mice exhibited markedly increased expression of GBP2, AIM2, Caspase-1, and GSDMD compared to controls. Following siRNA-mediated knockdown of\n Gbp2<\/jats:italic>\n in vitro, a consequent reduction was observed in pyroptosis-associated proteins (GSDMD, AIM2) and diminished secretion of the pro-inflammatory cytokines IL-1\u03b2 and IL-18. Conversely,\n Gbp2<\/jats:italic>\n overexpression aggravated these effects. Pyroptosis suppressed by\n Gbp2<\/jats:italic>\n knockdown was partially restored upon concurrent overexpression of\n Aim2<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Our results demonstrate that GBP2 expression is significantly upregulated in LN and promotes podocyte pyroptosis, likely contributing to renal injury. These findings suggest that GBP2 facilitates the progression of pediatric LN by activating the pyroptotic pathway and triggering the release of inflammatory cytokines.<\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0344601","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T17:22:11Z","timestamp":1773940931000},"page":"e0344601","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["GBP2 promotes podocyte pyroptosis and contributes to the pathogenesis of pediatric lupus 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nephritis","volume":"38","author":"HK Zhou","year":"2022","journal-title":"Chin J Immunol"},{"key":"pone.0344601.ref012","first-page":"775","article-title":"Bioinformatics analysis of gene expression microarray in lupus nephritis","volume":"20","author":"QZ Jiang","year":"2020","journal-title":"J Clin Nephrol"},{"issue":"3","key":"pone.0344601.ref013","doi-asserted-by":"crossref","first-page":"280","DOI":"10.3109\/08830185.2013.879711","article-title":"Emerging view of autophagy in systemic lupus erythematosus","volume":"34","author":"X-J Zhou","year":"2015","journal-title":"Int Rev Immunol"},{"issue":"1","key":"pone.0344601.ref014","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12865-022-00520-5","article-title":"GBP2 acts as a member of the interferon signalling pathway in lupus nephritis","volume":"23","author":"Y Zhang","year":"2022","journal-title":"BMC 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Quaglia","year":"2021","journal-title":"Viruses"},{"issue":"3","key":"pone.0344601.ref024","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1084\/jem.20182031","article-title":"Interferon-induced guanylate-binding proteins: Guardians of host defense in health and disease","volume":"216","author":"K Tretina","year":"2019","journal-title":"J Exp Med"},{"issue":"7","key":"pone.0344601.ref025","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1111\/j.1582-4934.2010.01146.x","article-title":"Role of guanylate binding protein-1 in vascular defects associated with chronic inflammatory diseases","volume":"15","author":"M Hammon","year":"2011","journal-title":"J Cell Mol Med"},{"issue":"1","key":"pone.0344601.ref026","doi-asserted-by":"crossref","first-page":"2250095","DOI":"10.1080\/08916934.2023.2250095","article-title":"Gbp3 is associated with the progression of lupus nephritis by regulating cell proliferation, inflammation and pyroptosis","volume":"56","author":"Z Zhang","year":"2023","journal-title":"Autoimmunity"},{"issue":"1","key":"pone.0344601.ref027","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1080\/08820139.2022.2122834","article-title":"GBP5 inhibition ameliorates the progression of lupus nephritis by suppressing NLRP3 inflammasome activation","volume":"52","author":"N Liu","year":"2023","journal-title":"Immunol Invest"},{"key":"pone.0344601.ref028","doi-asserted-by":"crossref","first-page":"1127612","DOI":"10.3389\/fimmu.2023.1127612","article-title":"GBP2 promotes M1 macrophage polarization by activating the notch1 signaling pathway in diabetic nephropathy","volume":"14","author":"X Li","year":"2023","journal-title":"Front Immunol"},{"issue":"12","key":"pone.0344601.ref029","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1002\/mc.23447","article-title":"GBP2 serves as a novel prognostic biomarker and potential immune microenvironment indicator in renal cell carcinoma","volume":"61","author":"Y Tian","year":"2022","journal-title":"Mol Carcinog"},{"issue":"1","key":"pone.0344601.ref030","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/s12882-025-04059-6","article-title":"Insights into pediatric lupus nephritis: clinical features and short-term outcomes from a single center retrospective study","volume":"26","author":"S Khatri","year":"2025","journal-title":"BMC Nephrol"},{"issue":"2","key":"pone.0344601.ref031","doi-asserted-by":"crossref","DOI":"10.1002\/iid3.70146","article-title":"Clinical and laboratory risk factors of early poor outcome in patients with childhood-onset lupus nephritis-a single-center retrospective study","volume":"13","author":"W Qijiao","year":"2025","journal-title":"Immun Inflamm Dis"},{"issue":"5","key":"pone.0344601.ref032","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3892\/mmr.2023.13091","article-title":"Immune podocytes in the immune microenvironment of lupus nephritis (Review)","volume":"28","author":"R Liu","year":"2023","journal-title":"Mol Med Rep"},{"issue":"6","key":"pone.0344601.ref033","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.kint.2016.01.012","article-title":"Podocyte injury and its consequences","volume":"89","author":"M Nagata","year":"2016","journal-title":"Kidney Int"},{"issue":"9","key":"pone.0344601.ref034","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.3390\/jcm8091340","article-title":"Podocyte injury in lupus nephritis","volume":"8","author":"H Sakhi","year":"2019","journal-title":"J Clin Med"},{"issue":"1","key":"pone.0344601.ref035","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1007\/s11926-024-01175-4","article-title":"The role of podocytes in lupus pathology","volume":"27","author":"K Maeda","year":"2024","journal-title":"Curr Rheumatol Rep"},{"issue":"4","key":"pone.0344601.ref036","doi-asserted-by":"crossref","first-page":"606","DOI":"10.34067\/KID.0000000688","article-title":"Podocyte injury and long-term kidney 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