{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T08:57:01Z","timestamp":1774342621218,"version":"3.50.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170664, 81870067"],"award-info":[{"award-number":["82170664, 81870067"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI), but specific therapeutic targets are lacking.Lysosomal Protein Transmembrane 4A (LAPTM4A), a four transmembrane-spanning protein mainly localized in endosomes and lysosomes,however, its pathological role in AKI remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate the impact of LAPTM4A on renal IRI, we developed an in vivo renal IRI model utilizing LAPTM4A knockout mice, alongside an in vitro hypoxia-reperfusion(H\/R) model employing shRNA to knockdown LAPTM4A in HK2 cell. A comprehensive suite of methodologies, including Western blotting, qPCR, CCK-8 assay, LDH assay, TUNEL assay, ELISA, and histopathological analysis, was employed to evaluate cell proliferation, apoptosis, and inflammatory cytokine levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found that the expression of Laptm4a was upregulated in kidney of renal IRI mice and HK2 cell induced by hypoxia-reoxygenation(H\/R). Knockout of Laptm4a improved renal function , attenuated tubular injury and reduced inflammatory cell infiltration and apoptosis, whereas overexpression exacerbated the injury.Mechanistically Laptm4a exacerbated renal IRI through suppression of the UNC5B-AKT-mTOR protective signaling pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings suggest that Laptm4a exacerbates inflammation and apoptosis by inhibiting the UNC5B-PI3K-AKT signaling pathway. This study provides a novel elucidation of the role of Laptm4a as a critical positive regulator of IRI, offering preliminary preclinical insights that may inform future investigations into therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1683343","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:24:44Z","timestamp":1774329884000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Laptm4a mediates renal ischemia-reperfusion injury by regulating the UNC5B-AKT\/mTOR signaling pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaoxiong","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan University","place":["Wuhan, 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