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Our transcriptional and histological analyses suggest that Gsdmd in tubulointerstitital cells may contribute to the pathogenesis of chronic oxalate nephropathy. However, genetic deletion of <jats:italic>Gsdmd<\/jats:italic> exacerbated oxalate nephropathy in mice in association with enhanced CaOx crystal deposition and accelerated tubular epithelial cell injury. Pharmacological inhibition of necroptosis reversed this effect. Indeed, <jats:italic>Gsdmd<\/jats:italic>\n            <jats:sup>\n              <jats:italic>\u2212\/\u2212<\/jats:italic>\n            <\/jats:sup> bone marrow-derived macrophages were more prone to undergo necroptosis when stimulated with CaOx crystals compared to their wildtype counterparts. We conclude that gasdermin D suppresses the necroptosis pathway, which determines the outcome of oxalate nephropathy-related nephrocalcinosis.<\/jats:p>","DOI":"10.1038\/s41419-025-07620-1","type":"journal-article","created":{"date-parts":[[2025,4,13]],"date-time":"2025-04-13T00:38:16Z","timestamp":1744504696000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Gasdermin D deficiency aggravates nephrocalcinosis-related chronic kidney disease with rendering macrophages vulnerable to necroptosis"],"prefix":"10.1038","volume":"16","author":[{"given":"Yoshihiro","family":"Kusunoki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanako","family":"Watanabe-Kusunoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meisi","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian Aurelio","family":"Marschner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6287-9725","authenticated-orcid":false,"given":"Andreas","family":"Linkermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5990-494X","authenticated-orcid":false,"given":"Stefanie","family":"Steiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2434-2956","authenticated-orcid":false,"given":"Hans-Joachim","family":"Anders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,13]]},"reference":[{"key":"7620_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.8","volume":"2","author":"SR Khan","year":"2016","unstructured":"Khan SR, Pearle MS, Robertson WG, Gambaro G, Canales BK, Doizi S, et al. 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