{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T06:37:56Z","timestamp":1787639876976,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300767"],"award-info":[{"award-number":["82300767"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260150"],"award-info":[{"award-number":["82260150"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070713"],"award-info":[{"award-number":["82070713"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Chronic kidney disease (CKD) remains a major global health challenge. Angiotensin II (Ang II)\u2010induced lipotoxicity is an important contributor to podocyte injury. Perilipin 5 (PLIN5) is a lipid droplet\u2010associated protein that helps maintain cellular metabolic homeostasis. However, how PLIN5 protects podocytes from lipotoxic stress remains incompletely understood. In this study, we generated podocyte\u2010specific PLIN5 knockout mice using the Cre\u2010loxP system and induced PLIN5 overexpression in\u00a0vivo and in\u00a0vitro. We found that Ang II markedly downregulated PLIN5 expression in podocytes both in\u00a0vivo and in\u00a0vitro. Podocyte\u2010specific deletion of PLIN5 aggravated Ang II\u2010induced lipid accumulation, mitochondrial dysfunction and apoptosis, whereas PLIN5 overexpression alleviated these abnormalities. Proteomic screening identified FK506\u2010binding protein 8 (FKBP8), an outer mitochondrial membrane protein, as a PLIN5\u2010interacting partner. Co\u2010immunoprecipitation and proximity ligation assays showed that the PLIN5\u2010FKBP8 interaction was reduced under Ang II stimulation. Functionally, FKBP8 knockdown disrupted lipid droplet\u2010mitochondria contact and exacerbated Ang II\u2010induced podocyte lipotoxicity. Domain\u2010mapping and rescue experiments further demonstrated that the 70\u2013200 amino acid region of FKBP8 is required for PLIN5 binding and for preservation of lipid droplet\u2010mitochondria contact under lipotoxic stress. In addition, disruption of the PLIN5\u2010FKBP8 axis was associated with impaired fatty acid utilisation and altered mitochondrial homeostasis. Collectively, these findings support a model in which PLIN5 protects podocytes, at least in part, by interacting with FKBP8 and preserving lipid droplet\u2010mitochondria contact, thereby limiting Ang II\u2010induced lipotoxic injury.<\/jats:p>","DOI":"10.1111\/cpr.70257","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:43:48Z","timestamp":1782866628000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>PLIN5<\/scp>\n                    Protects Against Ang\n                    <scp>II<\/scp>\n                    \u2010Induced Podocyte Lipotoxicity by Interacting With\n                    <scp>FKBP8<\/scp>\n                    and Preserving Lipid Droplet\u2013Mitochondria Contact"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7853-4086","authenticated-orcid":false,"given":"Ping","family":"Wang","sequence":"first","affiliation":[{"name":"Division of Nephrology Renmin Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Nephrology and Urology Research Institute of Wuhan University  Wuhan Hubei China"},{"name":"Division of Nephrology Jingmen Central Hospital Affiliated to Jingchu University of Technology  Jingmen Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Nephrology Renmin Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Nephrology and Urology Research Institute of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Ke","sequence":"additional","affiliation":[{"name":"Division of Nephrology Jingmen Central Hospital Affiliated to Jingchu University of Technology  Jingmen Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongtu","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Nephrology Renmin Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Nephrology and Urology Research Institute of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3244-8211","authenticated-orcid":false,"given":"Zhuan","family":"Peng","sequence":"additional","affiliation":[{"name":"Division of Nephrology Renmin Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Nephrology and Urology Research Institute of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Qi","sequence":"additional","affiliation":[{"name":"Division of Nephrology Renmin Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Nephrology and Urology Research Institute of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohua","family":"Ding","sequence":"additional","affiliation":[{"name":"Division of Nephrology Renmin Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Nephrology and Urology Research Institute of Wuhan University  Wuhan Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8847-845X","authenticated-orcid":false,"given":"Jijia","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Nephrology Renmin Hospital of Wuhan University  Wuhan Hubei China"},{"name":"Nephrology and Urology Research Institute of Wuhan University  Wuhan Hubei 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