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Nonsteroidal anti-inflammatory drug-activated gene (NAG-1), also known as growth differentiation factor 15 (GDF15), is a member of the transforming growth factor-\u03b2 superfamily and has been associated with anti-obesity properties and preservation of kidney function. While the NAG-1 sequence has been extensively studied in several species, a comprehensive understanding of feline NAG-1 remains limited. This study aimed to investigate the nucleotide sequence of feline NAG-1 and its biological role in kidney protection through in-vitro experiments.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>The feline <jats:italic>NAG-1<\/jats:italic> cDNA was isolated from the feline uterus, and its sequence was analyzed and compared to sequences from other species, including humans. Expression patterns of feline NAG-1 in various tissues, particularly the liver and kidney, were determined. Furthermore, the effects of different phytochemicals and NSAIDs known to induce NAG-1 expression were assessed using Crandell-Rees Feline Kidney (CRFK) cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The analysis revealed that feline NAG-1 shares similarities with human NAG-1 and exhibits high expression levels in the liver and kidney of cats. Treatment with tolfenamic acid, quercetin, and resveratrol significantly increased NAG-1 expression in CRFK cells. Subsequently, CRFK cells overexpressing feline NAG-1 were utilized to investigate the functional roles of NAG-1 in feline kidney health. High-content screening analysis demonstrated that NAG-1 overexpression in cat kidney cells enhanced mitochondrial membrane potential, reduced reactive oxygen species (ROS) generation in both whole cells and mitochondria, and downregulated the expression of Bax, a pro-apoptotic protein, under conditions of ROS-induced stress. These findings indicate the renoprotective role of NAG-1.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>This study highlights the significant role of NAG-1 in feline kidney cells, revealing its high expression in the liver and kidney and demonstrating its protective effects on kidney function. These results underscore the potential of NAG-1 as a key factor in kidney protection. Future research should focus on further elucidating the molecular pathways involved and exploring therapeutic strategies to harness NAG-1 for managing obesity-related renal dysfunction in cats.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12917-025-04781-1","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T03:12:54Z","timestamp":1747797174000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of feline nonsteroidal anti-inflammatory drug activated gene-1 (fNAG-1) and its protective function in kidney cells"],"prefix":"10.1186","volume":"21","author":[{"given":"Pattawika","family":"Lertpatipanpong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyunjin","family":"Moon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung Eun","family":"Seo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minsu","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Joon","family":"Baek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,21]]},"reference":[{"issue":"4","key":"4781_CR1","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/j.cvsm.2012.04.008","volume":"42","author":"JW Bartges","year":"2012","unstructured":"Bartges JW. 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Vet Sci 2021, 8(10).","DOI":"10.3390\/vetsci8100220"}],"container-title":["BMC Veterinary Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-025-04781-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12917-025-04781-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12917-025-04781-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T04:02:18Z","timestamp":1747800138000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcvetres.biomedcentral.com\/articles\/10.1186\/s12917-025-04781-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,21]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4781"],"URL":"https:\/\/doi.org\/10.1186\/s12917-025-04781-1","relation":{},"ISSN":["1746-6148"],"issn-type":[{"value":"1746-6148","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,21]]},"assertion":[{"value":"31 January 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"No approval of research ethics committees was required to accomplish the goals of this study in Korea because the tissues were obtained from the euthanized cat that was rescued from collapse. Informed verbal consent for the use of all animals in this study was obtained from the Gwanak-gu Office of the Seoul Metropolitan Government. An exemption from requiring ethics approval was granted by Seoul National University of Institutional Ethics Committee, as tissue was collected opportunistically postmortem from cats that were euthanized due to terminal illness unrelated to the research. No experimental procedures were conducted on live animals.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"364"}}