{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T22:20:55Z","timestamp":1768774855362,"version":"3.49.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,11]],"date-time":"2023-11-11T00:00:00Z","timestamp":1699660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20fk0108302"],"award-info":[{"award-number":["JP20fk0108302"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Nephrology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Circulated histones play a crucial role in the pathogenesis of infectious diseases and severe trauma, and it is one of the potential molecular targets for therapeutics. Recently, we reported that histone is one of the causative agents for urinary L\u2010FABP increase. However, the mechanism is still unclear, especially in severe cases. We further investigated the mechanism of urinary L\u2010FABP increase using a more severe mouse model with histone\u2010induced kidney injury. This study also aims to evaluate the therapeutic responsiveness of urinary L\u2010FABP as a preliminary study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Human L\u2010FABP chromosomal transgenic mice were administrated 30\u2009mg\/kg histone from a tail vein with a single dose. We also performed a comparative study in LPS administration model. For the evaluation of the therapeutic responsiveness of urinary L\u2010FABP, we used heparin and rolipram.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The histological change with cast formation as a characteristic of the models was observed in proximal tubules. Urinary L\u2010FABP levels were significantly elevated and these levels tended to be higher in those with more cast formation. Heparin and rolipram had the ameliorative effect of the cast formation induced by histone and urinary L\u2010FABP levels significantly decreased.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Histone is one of the causative agents for the increase of urinary L\u2010FABP at an early stage of AKI. In addition, it suggested that urinary L\u2010FABP may be useful as a subclinical AKI marker reflecting kidney damage induced by histone. Furthermore, urinary L\u2010FABP reflected the degree of the damage after the administration of therapeutic agents such as heparin and PDE4 inhibitor.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nep.14254","type":"journal-article","created":{"date-parts":[[2023,11,11]],"date-time":"2023-11-11T09:54:16Z","timestamp":1699696456000},"page":"117-125","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Urinary liver\u2010type fatty acid binding protein is a biomarker reflecting renal damage and the ameliorative effect of drugs at an early stage of histone\u2010induced <scp>acute kidney injury<\/scp>"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5635-4292","authenticated-orcid":false,"given":"Keiichi","family":"Ohata","sequence":"first","affiliation":[{"name":"Department of Nutritional Science and Food Safety, Faculty of Applied Biosciences Tokyo University of Agriculture  Tokyo 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