{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:41:14Z","timestamp":1790185274935,"version":"4.1.0"},"reference-count":42,"publisher":"SAGE Publications","issue":"7-9","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Postgraduate Research and Practice Innovation Program of Harbin Medical University","award":["Grant No. YJSCX2024-28HYD"],"award-info":[{"award-number":["Grant No. YJSCX2024-28HYD"]}]},{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"crossref","award":["Grant No. PL2024H042"],"award-info":[{"award-number":["Grant No. PL2024H042"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Outstanding Young Medical Talent Training Program of the First Affiliated Hospital of Harbin Medical University","award":["Grant No. HYD2020JQ0020"],"award-info":[{"award-number":["Grant No. HYD2020JQ0020"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["Grant No. 82473337"],"award-info":[{"award-number":["Grant No. 82473337"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>Nephron-sparing surgery (NSS) is associated with acute kidney injury (AKI) that can accelerate chronic kidney disease progression, yet the mechanisms driving NSS-related injury (NRI) remain incompletely understood. In particular, how surgical stress reprograms proximal tubular energy metabolism independent of persistent ischemia remains unresolved. This study aimed to elucidate the mechanisms underlying lipid metabolic dysregulation and mitochondrial dysfunction in NRI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Clinical cohort analysis showed that prolonged warm ischemia time was independently associated with postoperative AKI. Across human and experimental NRI, proximal tubular cells exhibited consistent suppression of fatty acid oxidation, increased lipid accumulation, and mitochondrial dysfunction. These metabolic abnormalities were associated with increased protein phosphatase 2A (PP2A) activity, reduced extracellular signal-regulated kinase (ERK) phosphorylation, and diminished transcriptional activity of the peroxisome proliferator-activated receptor-alpha (PPAR\u2013\u03b1)\/PGC-1\u03b1 metabolic axis. Experimental modulation of PP2A or restoration of ERK-dependent PPAR-\u03b1 signaling partially rescued mitochondrial function, reduced lipotoxic stress, and attenuated tubular injury. Single-cell and cell-type-resolved analyses localized these changes predominantly to metabolically active proximal tubular subpopulations, supporting the cell-type specificity of this pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation and Conclusion:<\/jats:title>\n                    <jats:p>\n                      This study identifies PP2A-dependent suppression of ERK\u2013PPAR-\u03b1\/PGC-1\u03b1 signaling as a central mechanism underlying proximal tubular metabolic failure in NRI. By linking surgical stress to disordered lipid metabolism, these findings reveal a previously underappreciated regulatory pathway distinct from classical ischemic injury and highlight tubular metabolic resilience as a therapeutic target for mitigating kidney injury following nephron-sparing surgery.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      45, 315\u2013337.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864261455422","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:26:42Z","timestamp":1780374402000},"page":"315-337","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["PP2A\u2013ERK\u2013PPAR-\u03b1\/PGC-1\u03b1 Axis Drives Tubular Lipotoxicity and Mitochondrial Dysfunction in Nephron-Sparing Surgery-Related Acute Kidney Injury"],"prefix":"10.1177","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8798-7711","authenticated-orcid":false,"given":"Haoxun","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China."},{"name":"Department of Central Laboratory, Harbin Medical University State-Province Key Laboratory, Harbin, China."},{"name":"The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, First Affiliated Hospital of Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China."},{"name":"Department of Central Laboratory, Harbin Medical University State-Province Key Laboratory, Harbin, China."},{"name":"The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, First Affiliated Hospital of Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China."},{"name":"The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, First Affiliated Hospital of Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China."},{"name":"The Key Laboratory of Cardiovascular Disease Acousto-Optic Electromagnetic Diagnosis and Treatment in Heilongjiang Province, First Affiliated Hospital of Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuran","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"issue":"6","key":"e_1_3_4_2_1","first-page":"739","article-title":"On-clamp versus purely off-clamp robot-assisted partial nephrectomy in solitary kidneys: Comparison of perioperative outcomes and chronic kidney disease progression at two high-volume centers","volume":"73","author":"Anceschi U","year":"2021","unstructured":"Anceschi U, , Brassetti A, , Bertolo R, et al. 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