{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T17:59:38Z","timestamp":1776448778558,"version":"3.51.2"},"reference-count":24,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical and Health Technology Project of Shandong Province","award":["202402050122"],"award-info":[{"award-number":["202402050122"]}]},{"name":"Science and Technology Development Plan of Jinan Municipal Health Commission","award":["2024301008"],"award-info":[{"award-number":["2024301008"]}]},{"name":"Clinical Medical Science and Technology Innovation Program of Jinan Science and Technology Bureau","award":["202430055"],"award-info":[{"award-number":["202430055"]}]},{"name":"Science and Technology Development Plan of Jinan Municipal Health Commission","award":["2024201005"],"award-info":[{"award-number":["2024201005"]}]},{"name":"Clinical Medical Science and Technology Innovation Program of Jinan Science and Technology Bureau","award":["202328011"],"award-info":[{"award-number":["202328011"]}]},{"name":"Special Fund for High level Talents in the Medical and Health Industry of Jinan City","award":["202412"],"award-info":[{"award-number":["202412"]}]},{"name":"Taishan Scholar Special Funding","award":["tsqnz20240858"],"award-info":[{"award-number":["tsqnz20240858"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Diabetic nephropathy (DN) is a major diabetic complication, and while DJ-1 has been shown to mitigate renal ischemia\/reperfusion injury, its role in high glucose-induced podocyte damage remains unclear. This study aimed to investigate the function and mechanism of DJ-1 in high glucose-induced injury of human podocyte cells (HPCs). Using RNA-seq analysis, we identified that high glucose broadly affected multiple signaling pathways related to cell growth, death, and signal transduction. Notably, DJ-1 expression was downregulated under high glucose conditions. Overexpression of DJ-1 significantly attenuated high glucose-induced HPC\u00a0apoptosis. Mechanistically, DJ-1 promoted the phosphorylation of ERK1\/2 and facilitated the nuclear translocation of p-ERK1\/2. This activated the ERK1\/2 pathway and upregulated the expression of NF-\u03baB p65 and AP-1, thereby suppressing HPC\u00a0apoptosis under high glucose conditions. In summary, our findings reveal that DJ-1 protects against high glucose-induced HPC\u00a0injury by activating the ERK1\/2 pathway and enhancing NF-\u03baB p65 and AP-1 expression, providing new insights into the molecular mechanisms of DJ-1 in diabetic nephropathy.<\/jats:p>","DOI":"10.1371\/journal.pone.0346714","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T17:22:32Z","timestamp":1776446552000},"page":"e0346714","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["DJ-1 alleviates high glucose-induced podocyte injury via activating ERK1\/2 signaling"],"prefix":"10.1371","volume":"21","author":[{"given":"Xiaochen","family":"Tian","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6540-0943","authenticated-orcid":true,"given":"Leisheng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0189-0187","authenticated-orcid":true,"given":"Ping","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1056-1317","authenticated-orcid":true,"given":"Yusheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"pone.0346714.ref001","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.cytogfr.2025.05.007","article-title":"Exploring 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