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We previously reported that glucosylceramide (GlcCer) acts as a damage-associated molecular pattern (DAMP) during AKI. Here, we demonstrate that renal GlcCer levels increase persistently during AKI, primarily due to oxidative stress-mediated downregulation of \u03b2-1,4-galactosyltransferase 5 (B4galt5) in proximal tubules. Using mass spectrometry, we showed that GlcCer specifically accumulated in damaged proximal tubules. Among the enzymes involved in GlcCer metabolism, B4galt5 was predominantly expressed in proximal tubules and its expression was consistently downregulated across multiple AKI models. Knockdown of B4galt5 alone was sufficient to increase GlcCer levels in cultured proximal tubular cells. Moreover, in vivo administration of GlcCer combined with free cholesterol triggered inflammatory responses via the innate immune receptor macrophage-inducible C-type lectin (Mincle). These inflammatory responses were almost abolished in Mincle-deficient mice, suggesting a specific GlcCer-Mincle pathway. Our findings indicate that B4galt5 plays a critical role in GlcCer accumulation in necrotic tubules following AKI. Specifically, we propose that dying proximal tubules alter their glycolipid metabolism to generate DAMPs, highlighting B4galt5 as a potential therapeutic target for preventing the AKI-to-CKD transition.<\/jats:p>","DOI":"10.1038\/s41598-025-28897-4","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T21:19:07Z","timestamp":1764710347000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Altered glycolipid metabolism during acute kidney injury exacerbates renal inflammation"],"prefix":"10.1038","volume":"16","author":[{"given":"Akinori","family":"Osada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyako","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Sugiura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunmei","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Yamashita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kozue","family":"Ochi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiro","family":"Kohda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiori","family":"Go","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Okajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Kadomatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoko","family":"Yanagita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Furuhashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoichi","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayoshi","family":"Suganami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"28897_CR1","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/S0272-6386(12)81128-0","volume":"17","author":"J Kaufman","year":"1991","unstructured":"Kaufman, J., Dhakal, M., Patel, B. & Hamburger, R. 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