{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:24:00Z","timestamp":1787822640343,"version":"build-2784847793"},"reference-count":80,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,8,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Renal fibrosis is a final pathway leading to end\u2010stage renal disease, with cellular senescence contributing to fibrosis and inflammation. Magnesium ions (Mg\n                    <jats:sup>2+<\/jats:sup>\n                    ) are implicated in DNA stabilization and epigenetic regulation. In this study, we hypothesized that Mg\n                    <jats:sup>2+<\/jats:sup>\n                    ameliorates renal fibrosis in association with reduced DNA damage responses and injury\u2010induced cellular senescence, along with altered histone H3K4 trimethylation. To test this, we used murine models of radiation\u2010induced organ injury and renal ischemia\u2013reperfusion injury (IRI), along with primary cultured mouse renal proximal tubular cells. Mice received intraperitoneal MgSO\n                    <jats:sub>4<\/jats:sub>\n                    (600\u2009mg\/kg) before radiation or IRI, with repeated dosing (300\u2009mg\/kg) after IRI. Cultured cells were treated with 6.4\u2009mM MgSO\n                    <jats:sub>4<\/jats:sub>\n                    . We demonstrated that Mg\n                    <jats:sup>2+<\/jats:sup>\n                    provided protection against radiation injury and reduced radiation\u2010induced DNA damage markers in renal cells both in\u00a0vitro and in\u00a0vivo. Furthermore, Mg\n                    <jats:sup>2+<\/jats:sup>\n                    suppressed IRI\u2010induced morphological alterations, DNA damage, and cellular senescence in the kidneys, while inhibiting renal inflammation and cGAS\u2010STING pathway activation, along with attenuation of renal fibrosis in IRI model mice. Consistent with these findings, a reduction in the expression of pro\u2010inflammatory cytokines and fibrosis\u2010related genes was observed. Finally, Mg\n                    <jats:sup>2+<\/jats:sup>\n                    was associated with decreased p16\n                    <jats:sup>INK4a<\/jats:sup>\n                    transcription and reduced H3K4 trimethylation levels at its promoter in primary renal tubular cells. Our findings suggest that Mg\n                    <jats:sup>2+<\/jats:sup>\n                    alleviates renal DNA damage while protecting against inflammation and fibrosis with accompanying epigenetic modulation. Although clinically relevant pharmacological Mg\n                    <jats:sup>2+<\/jats:sup>\n                    dosing and therapeutic applicability require further investigation, these insights may inform therapeutic strategies targeting fibrosis and senescence\u2010related kidney disease.\n                  <\/jats:p>","DOI":"10.1096\/fj.202504665rr","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T18:05:46Z","timestamp":1786730746000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Magnesium Attenuates Renal Senescence and Fibrosis With Reduced\n                    <scp>DNA<\/scp>\n                    Damage Response and\n                    <scp>H<\/scp>\n                    3\n                    <scp>K<\/scp>\n                    4me3 Enrichment at the\n                    <i>\n                      p16\n                      <sup>INK4a<\/sup>\n                    <\/i>\n                    Promoter"],"prefix":"10.1096","volume":"40","author":[{"given":"Makoto","family":"Matsubara","sequence":"first","affiliation":[{"name":"Department of Nephrology Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5899-0885","authenticated-orcid":false,"given":"Kensuke","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Nephrology Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigehiro","family":"Doi","sequence":"additional","affiliation":[{"name":"Department of Nephrology Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Ike","sequence":"additional","affiliation":[{"name":"Department of Nephrology Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Nephrology Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Nephrology Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Osaki","sequence":"additional","affiliation":[{"name":"Department of Nephrology Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Ishiuchi","sequence":"additional","affiliation":[{"name":"Department of Nephrology Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiko","family":"Okubo","sequence":"additional","affiliation":[{"name":"Department of Nephrology Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiro","family":"Maeoka","sequence":"additional","affiliation":[{"name":"Department of Nephrology Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuto","family":"Chiba","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Pediatrics University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayumu","family":"Nakashima","sequence":"additional","affiliation":[{"name":"Department of Nephrology Hiroshima University Hospital  Hiroshima Japan"},{"name":"Department of Nephrology, Graduate School of Medicine University of Yamanashi  Yamanashi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Masaki","sequence":"additional","affiliation":[{"name":"Department of Nephrology Hiroshima University Hospital  Hiroshima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30045-3"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-024-00820-6"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kisu.2021.11.003"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.08.025"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0248-y"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-022516-034227"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-022-00590-z"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2023.09.001"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01379-7"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.05.039"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2016.11.006"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.116"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2019.06.021"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.564461"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3558"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00524-z"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1705499114"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.08.003"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0027-5107(01)00074-4"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng889"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241210100"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.12.035"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00012.2014"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20174232"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.100339"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2020.11.002"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9040319"},{"key":"e_1_2_10_29_1","first-page":"1","article-title":"Magnesium Suppresses In\u00a0Vivo Oxidative Stress and Ex\u00a0Vivo DNA Damage Induced by Protracted ACTH Treatment in Rats","volume":"36","author":"\u0110uri\u0107 V.","year":"2023","journal-title":"Magnesium Research"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2015.165"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.02.006"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1411-0"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.78"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI158446"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202402382R"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22189949"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu16040496"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3959(93)90225-E"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlx073"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22084253"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1995.tb12035.x"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2013.08.028"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkw752"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014090850"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.158754"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.122.19159"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2020071010"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2015.291"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-74340-5"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.135454"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.171961"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.5142\/jgr.2011.35.3.261"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1162546"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152153"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.09.050"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075622"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0161079"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-07426-7"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-025-00934-5"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00775-0"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00694-0"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-022-03118-3"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200209270-00009"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jss.2013.01.040"},{"key":"e_1_2_10_65_1","first-page":"74","article-title":"Magnesium Enhances Cardiomyocyte Proliferation and Suppresses Cardiac Fibrosis Induced by Chronic ACTH Exposure in Rats","volume":"34","author":"Petrovi\u0107 J.","year":"2021","journal-title":"Magnesium Research"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3823"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-018-0712-x"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2016.183"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014111059"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00044.x"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2011100967"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712401105"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-022-02182-4"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202012423"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1229963"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjab066"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2012.11.012"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.6.5.15220"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2024.168671"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-025-02668-x"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080874"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202504665RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202504665RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202504665RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:15:10Z","timestamp":1787822110000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202504665RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":80,"journal-issue":{"issue":"16","published-print":{"date-parts":[[2026,8,31]]}},"alternative-id":["10.1096\/fj.202504665RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.202504665rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]},"assertion":[{"value":"2025-12-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72192"}}