{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:36:00Z","timestamp":1786700160829,"version":"build-2736575974"},"reference-count":44,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82570823"],"award-info":[{"award-number":["82570823"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82570823"],"award-info":[{"award-number":["82570823"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Acute kidney injury (AKI) is a critical clinical syndrome with limited effective therapies, in which renal tubular epithelial cell (RTEC) pyroptosis mediated by the NLRP3 inflammasome represents an important pathological contributor. Stress granules (SGs), dynamic membrane-less condensates, enable cells to adapt to various stress conditions, yet their role and regulatory mechanism in AKI remain unclear. Here, we identify SG persistence as a protective mechanism against AKI and show that poly(ADP-ribosyl)ation (PARylation)-mediated regulation of SG dynamics alleviates pyroptosis during renal injury. We found that SGs were prominently formed in RTECs from AKI patients, cisplatin-induced AKI mice, and cisplatin-stimulated HK-2 cells. Poly(ADP-ribose) glycohydrolase (PARG), the key enzyme for reversing PARylation, was significantly upregulated in injured renal tissues and cells. Genetic or pharmacological inhibition of PARG delayed SG disassembly, enhanced SG persistence, and mitigated renal injury. Mechanistically, persistent SGs regulated DDX3X availability and reduced DDX3X-NLRP3 inflammasome activation, thereby attenuating RTEC pyroptosis. These findings uncover a novel mechanism of SG-mediated renoprotection and highlight SG dynamics as a potential therapeutic target in AKI.<\/jats:p>","DOI":"10.3390\/ijms27167192","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T07:57:26Z","timestamp":1786521446000},"page":"7192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Delaying Stress Granule Disassembly by PARG Inhibition Attenuates Renal Tubular Cell Pyroptosis in Acute Kidney Injury"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2374-9642","authenticated-orcid":false,"given":"Yiyun","family":"Song","sequence":"first","affiliation":[{"name":"Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinchai","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banghuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"},{"name":"Department of Nephrology, Chongqing Hospital Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Chongqing 401121, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1186\/cc11454","article-title":"Diagnosis, evaluation, and management of acute kidney injury: A KDIGO summary (Part 1)","volume":"17","author":"Kellum","year":"2013","journal-title":"Crit. 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Neurodegener."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7192\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T09:04:38Z","timestamp":1786698278000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/16\/7192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,12]]},"references-count":44,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ijms27167192"],"URL":"https:\/\/doi.org\/10.3390\/ijms27167192","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,12]]}}}