{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:52:27Z","timestamp":1789671147056,"version":"4.0.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T00:00:00Z","timestamp":1705622400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U23A20410"],"award-info":[{"award-number":["U23A20410"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300806"],"award-info":[{"award-number":["82300806"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Young and Middle-aged Scientific Research Major Project of Fujian Provincial Health Commission","award":["2021ZQNZD004"],"award-info":[{"award-number":["2021ZQNZD004"]}]},{"name":"Joint Funds for the Innovation of Science and Technology of Fujian Province","award":["2021Y9100"],"award-info":[{"award-number":["2021Y9100"]}]},{"name":"Fujian Province Finance Project","award":["2020B009"],"award-info":[{"award-number":["2020B009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and hypothesis<\/jats:title>\n                    <jats:p>Acute kidney injury (AKI) could progress to chronic kidney disease (CKD) and the AKI-CKD transition has major clinical significance. A growing body of evidence has unveiled the role of pyroptosis in kidney injury. We postulate that GSDMD and GSDME exert cumulative effects on the AKI-CKD transition by modulating different cellular responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We established an AKI-CKD transition model induced by folic acid in wildtype (WT), Gsdmd\u2212\/\u2212, Gsdme\u2212\/\u2212, and Gsdmd\u2212\/\u2212Gsdme\u2212\/\u2212 mice. Tubular injury, renal fibrosis and inflammatory responses were evaluated. In vitro studies were conducted to investigate the interplay among tubular cells, neutrophils, and macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Double deletion of Gsdmd and Gsdme conferred heightened protection against AKI, mitigating inflammatory responses, including the formation of neutrophil extracellular traps (NETs), macrophage polarization and differentiation, and ultimately renal fibrosis, compared with wildtype mice and mice with single deletion of either Gsdmd or Gsdme. Gsdme, but not Gsdmd deficiency, shielded tubular cells from pyroptosis. GSDME-dependent tubular cell death stimulated NETs formation and prompted macrophage polarization towards a pro-inflammatory phenotype. Gsdmd deficiency suppressed NETs formation and subsequently hindered NETs-induced macrophage-to-myofibroblast transition (MMT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GSDMD and GSDME collaborate to contribute to AKI and subsequent renal fibrosis induced by folic acid. Synchronous inhibition of GSDMD and GSDME could be an innovative therapeutic strategy for mitigating the AKI-CKD transition.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfae014","type":"journal-article","created":{"date-parts":[[2024,1,18]],"date-time":"2024-01-18T15:17:19Z","timestamp":1705591039000},"page":"1344-1359","source":"Crossref","is-referenced-by-count":30,"title":["GSDMD and GSDME synergy in the transition of acute kidney injury to chronic kidney disease"],"prefix":"10.1093","volume":"39","author":[{"given":"Zhengyue","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical University , Fuzhou , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Blood Purification Research Center, The First Affiliated Hospital, Fujian Medical 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