{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:52:17Z","timestamp":1791478337162,"version":"4.3.4"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Sepsis-associated AKI is a life-threatening condition associated with profound metabolic dysfunction, including impaired mitochondrial fatty acid handling. Therapies capable of reversing this metabolic dysfunction remain lacking. Using a clinically relevant porcine model, we investigated whether kidney-targeted fibroblastic reticular cell-derived and CD5L-enriched exosomes could ameliorate sepsis-associated AKI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We generated engineered exosomes derived from fibroblastic reticular cells or CD5L-overexpressing cells and functionalized them with the kidney-targeting LTH peptide. Therapeutic efficacy and safety were evaluated in a porcine model of lipopolysaccharide-induced sepsis-associated AKI. Integrated multiomic and cellular analyses were performed to examine the associated molecular pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>In septic pigs, both fibroblastic reticular cell-derived and CD5L-enriched exosomes improved systemic hemodynamics, renal microvascular perfusion, and kidney injury indices. Exosome treatment reduced renal lipid-droplet and acylcarnitine accumulation. CD5L interacted with fatty acid synthase, and treatment was associated with changes in short-chain fatty acids and AMPK-ACC-CPT1A signaling. These lipid-metabolic changes were accompanied by improved mitochondrial bioenergetic indices, preserved mitochondrial morphology, and reduced markers of tubular cell pyroptosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Kidney-targeted fibroblastic reticular cell-derived and CD5L-enriched exosomes produced comparable improvements in kidney injury indices and were associated with renal lipid-metabolic and mitochondrial remodeling in a large-animal model of sepsis-associated AKI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.0000001266","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:03:13Z","timestamp":1791475393000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Fibroblastic Reticular Cell\u2013Derived and CD5L-Enriched Exosomes Remodel Renal Lipid Metabolism in Porcine Sepsis\u2013Associated Acute Kidney Injury"],"prefix":"10.1681","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0236-9840","authenticated-orcid":false,"given":"Yiming","family":"Li","sequence":"first","affiliation":[{"name":"Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China;"},{"name":"Clinical Research Center of Hubei, Critical Care Medicine, Wuhan, 430071, Hubei, China;"},{"name":"Department of Intensive Care Unit, Shenzhen Guangming District People's Hospital, 518000, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5613-0478","authenticated-orcid":false,"given":"Wen","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine, Affiliated Central People's Hospital, China Three Gorges University, Yichang, 443003, Hubei, China;"},{"name":"The First College of Clinical Medical Science, China Three Gorges University, Yichang, 443003, Hubei, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongxue","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China;"},{"name":"Clinical Research Center of Hubei, Critical Care Medicine, Wuhan, 430071, Hubei, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5432-9570","authenticated-orcid":false,"given":"Pan","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese Medicine and Western Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China;"},{"name":"Clinical Research Center of Hubei, Critical Care Medicine, Wuhan, 430071, Hubei, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmeng","family":"Suo","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China;"},{"name":"Clinical Research Center of Hubei, Critical Care Medicine, Wuhan, 430071, Hubei, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2628-8362","authenticated-orcid":false,"given":"Yusheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Emergency and Critical Care Medicine, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441021, Hubei, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2970-7878","authenticated-orcid":false,"given":"Xiaoyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China;"},{"name":"Clinical Research Center of Hubei, Critical Care Medicine, Wuhan, 430071, Hubei, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430071, Hubei, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaocheng","family":"Weng","sequence":"additional","affiliation":[{"name":"College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430071, Hubei, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2949-0811","authenticated-orcid":false,"given":"Timothy R.","family":"Billiar","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, 15260, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1995-2653","authenticated-orcid":false,"given":"John A.","family":"Kellum","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, 15260, USA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China;"},{"name":"Clinical Research Center of Hubei, Critical Care Medicine, Wuhan, 430071, Hubei, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4465-9814","authenticated-orcid":false,"given":"Bo","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China;"},{"name":"Clinical Research Center of Hubei, Critical Care Medicine, Wuhan, 430071, Hubei, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0849-5648","authenticated-orcid":false,"given":"Zhiyong","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China;"},{"name":"Clinical Research Center of Hubei, Critical Care Medicine, Wuhan, 430071, Hubei, China;"},{"name":"Department of Intensive Care Unit, Shenzhen Guangming District People's Hospital, 518000, Shenzhen, China."},{"name":"Intensive Care Unit of the second affiliated Hospital of Hainan Medical College, Haikou, Hainan, 570105, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,10,8]]},"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001266","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:03:14Z","timestamp":1791475394000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001266"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1681\/asn.0000001266","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]},"assertion":[{"value":"2026-01-13","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-25","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}