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Arachidonic acid (AA), an inflammatory lipid mediator released during tissue injury and infection, has been implicated in podocyte injury, but its contribution to metabolic dysfunction in MCD remains unclear. Here, we investigated whether AA aggravates PAN\u2010induced podocyte injury and examined the involvement of pyruvate kinase M2 (PKM2)\u2010associated metabolic dysfunction. In a puromycin aminonucleoside (PAN)\u2010induced rat model, AA exposure increased serum AA levels, aggravated proteinuria, reduced nephrin expression, promoted foot\u2010process effacement and exacerbated mitochondrial dysfunction. AA was also associated with reduced PKM1 and PKM2 abundance, increased PKM2 (Tyr105) phosphorylation, decreased pyruvate kinase activity and lower pyruvate, lactate and ATP levels. In cultured human podocytes, AA intensified PAN\u2010induced cytoskeletal disruption, mitochondrial dysfunction, oxidative stress and apoptosis. Pharmacological activation of PKM2 with TEPP\u201046 partially restored PK\u2010associated metabolic activity, improved mitochondrial readouts and attenuated podocyte injury in\u00a0vitro. These findings suggest that AA exacerbates PAN\u2010induced podocyte injury in association with PKM2\u2010associated metabolic dysfunction and mitochondrial stress.<\/jats:p>","DOI":"10.1111\/jcmm.71404","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:51:50Z","timestamp":1791773510000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Arachidonic Acid Disrupts\n                    <scp>PKM2<\/scp>\n                    \u2010Linked Glycolysis\u2010Related Metabolism and Exacerbates\n                    <scp>PAN<\/scp>\n                    \u2010Induced Podocyte Injury"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9632-3183","authenticated-orcid":false,"given":"Kun","family":"Nie","sequence":"first","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou 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Kidney Disease, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjie","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9816-7842","authenticated-orcid":false,"given":"Jiaqun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyi","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Fujian Clinical Research Center for Metabolic Chronic Kidney Disease, The First Affiliated Hospital Fujian Medical University  Fuzhou China"},{"name":"Department of Nephrology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital Fujian Medical University  Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2586-1363","authenticated-orcid":false,"given":"Yongjie","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital Fujian Medical University  Fuzhou 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