{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:05:58Z","timestamp":1791223558685,"version":"4.1.0"},"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T00:00:00Z","timestamp":1751846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Medical and Health Science and Technology Development Plan Project of Shandong Province, China","award":["202203050656"],"award-info":[{"award-number":["202203050656"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Chronic kidney disease (CKD) is a global health issue that significantly threatens human health, with its incidence increasing annually. Renal fibrosis is characterized by the progressive loss of kidney function, leading to significant morbidity and mortality. Although ribosome biogenesis has been reported to be increased in several kidney diseases, its role in renal fibrosis remains unclear. This study investigates the role of the interferon-stimulated gene of 20\u2009kDa protein (<jats:italic>Isg20<\/jats:italic>), an RNA exonuclease involved in several stages of ribosome biogenesis, in the progression of renal fibrosis. Bioinformatics analysis of Gene Expression Omnibus (GEO) datasets identified upregulation of ribosome biogenesis-related genes and <jats:italic>Isg20<\/jats:italic> expression in renal fibrosis samples. Using the unilateral ureteral obstruction (UUO)-induced renal fibrosis mouse model, we confirmed elevated <jats:italic>Isg20<\/jats:italic> expression, promoted renal fibrosis, and increased ribosome biogenesis. Knockdown of <jats:italic>Isg20<\/jats:italic> significantly reduced ribosome biogenesis, ameliorated kidney damage, inhibited pro-inflammatory cytokines levels and renal fibrotic changes, and decreased endoplasmic reticulum stress and cell apoptosis. Our findings suggest that <jats:italic>Isg20<\/jats:italic> exacerbates renal fibrosis by promoting ribosome biogenesis, ER stress and cell apoptosis highlighting a potential therapeutic target for renal fibrosis treatment.<\/jats:p>","DOI":"10.1371\/journal.pone.0322639","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T17:23:38Z","timestamp":1751909018000},"page":"e0322639","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting interferon-stimulated gene of 20\u2009kDa protein (Isg20) inhibits ribosome biogenesis to ameliorate the progression of renal 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Ma","year":"2024","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"pone.0322639.ref023","doi-asserted-by":"crossref","first-page":"190","DOI":"10.21037\/atm-22-366","article-title":"Identification of key biomarkers and immune infiltration in renal interstitial fibrosis","volume":"10","author":"Z Hu","year":"2022","journal-title":"Ann Transl Med"},{"issue":"2","key":"pone.0322639.ref024","doi-asserted-by":"crossref","DOI":"10.1093\/bib\/bbae023","article-title":"Genomic hallmarks and therapeutic targets of ribosome biogenesis in cancer","volume":"25","author":"Y Zang","year":"2024","journal-title":"Brief Bioinform"},{"issue":"1","key":"pone.0322639.ref025","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1172\/JCI93560","article-title":"Endoplasmic reticulum stress in the pathogenesis of fibrotic disease","volume":"128","author":"JA Kropski","year":"2018","journal-title":"J Clin 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analysis","volume":"2022","author":"Y-C Sun","year":"2022","journal-title":"J Immunol Res"},{"issue":"6","key":"pone.0322639.ref036","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1046\/j.1523-1755.1998.00210.x","article-title":"Treatment of acute renal failure","volume":"54","author":"RA Star","year":"1998","journal-title":"Kidney Int"},{"issue":"3","key":"pone.0322639.ref037","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1053\/j.ackd.2008.04.003","article-title":"Biomarkers of acute kidney injury","volume":"15","author":"CL Edelstein","year":"2008","journal-title":"Adv Chronic Kidney Dis"},{"issue":"2","key":"pone.0322639.ref038","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/j.2040-4603.2012.tb00431.x","article-title":"Pathophysiology of acute kidney injury","volume":"2","author":"DP Basile","year":"2012","journal-title":"Compr 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