{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T01:51:57Z","timestamp":1785289917362,"version":"3.55.0"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Acute kidney injury (AKI), a prevalent complication of sepsis, sorely needs effective interventions. Yet, our grasp of the mechanisms behind sepsis\u2010induced AKI is far from complete, hindering the development of targeted therapies. Cecal ligation and puncture (CLP) was used to induce sepsis in mice, followed by treatment with the PLK3 antagonist R406 to assess the effects of PLK3 inhibition on inflammatory responses and renal damage. A lipopolysaccharide (LPS)\u2010induced injury model in HK\u20102 cells was developed to explore the impact of LPS on lysosomal membrane permeability (LMP) and PLK3 expression. Knocking down PLK3 in HK\u20102 cells, we investigated its effects on cell viability, apoptosis, mitochondrial membrane potential (MMP), and mitochondrial reactive oxygen species (mtROS). Through bioinformatics analysis, the upstream transcription factor of PLK3 was screened and identified as MAF BZIP transcription factor F (MAFF). The transcriptional regulatory relationship was validated, and rescue experiments were conducted to investigate the effects of MAFF upregulating PLK3 on cell viability and apoptosis. In our study, inhibiting PLK3 in CLP mice mitigated kidney injury, as evidenced by reduced Scr, BUN, and KIM\u20101 levels, alongside suppressed cell apoptosis, increased pro\u2010inflammatory cytokines, and reduced oxidative stress. In LPS\u2010stimulated HK\u20102 cells, PLK3 expression was markedly higher, leading to reduced cell viability and increased lysosomal permeability. Knocking down PLK3 in these cells effectively reversed the LPS\u2010induced effects, including cell apoptosis, MMP decrease, and mtROS accumulation. Finally, the upstream transcription factor of PLK3, MAFF, was identified and confirmed to transcriptionally activate PLK3 expression. The upregulation of PLK3 by MAFF further suppressed cell viability and promoted apoptosis in LPS\u2010treated HK\u20102 cells. PLK3 is a key driver of sepsis\u2010associated AKI (S\u2010AKI), transcriptionally activated by MAFF, and mediates its effects through the mitochondrial apoptotic pathway. Targeting PLK3 could be an effective strategy to reduce the impact of S\u2010AKI.<\/jats:p>","DOI":"10.1002\/jbt.70462","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T12:21:22Z","timestamp":1756383682000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["PLK3\u2010Activated Mitochondrial Apoptosis Pathway in the Pathogenesis of Sepsis\u2010Associated Acute Kidney Injury"],"prefix":"10.1002","volume":"39","author":[{"given":"Pinlu","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Emergency Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University  Linhai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University  Linhai 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