{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:35:52Z","timestamp":1785418552992,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Technologies R&D Program of China","award":["2022YFC3602300"],"award-info":[{"award-number":["2022YFC3602300"]}]},{"name":"National Key Technologies R&D Program of China","award":["2022YFC3602303"],"award-info":[{"award-number":["2022YFC3602303"]}]},{"DOI":"10.13039\/501100004829","name":"Foundation of Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["2022YFS0297"],"award-info":[{"award-number":["2022YFS0297"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Foundation of Science and Technology Department of Sichuan Province","doi-asserted-by":"publisher","award":["2022YFS0326"],"award-info":[{"award-number":["2022YFS0326"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004912","name":"Sichuan University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004912","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/011ashp19","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Foundation of the National Research Center of Geriatrics","award":["Y2018A32"],"award-info":[{"award-number":["Y2018A32"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetic kidney disease (DKD) is a primary cause of end-stage renal disease (ESRD), and while ferroptosis is known to contribute to DKD pathogenesis, the regulatory role of the NLRP3 inflammasome in this process remains elusive. To address this research gap, we explored whether NLRP3 inhibition alleviates DKD by suppressing ferroptosis using streptozotocin-induced diabetic wild-type and NLRP3-knockout C57BL\/6 mice, alongside high-glucose-cultured (30 mM) human renal tubular epithelial (HK-2) cells with or without siNLRP3 transfection. Inflammatory cytokines (IL-6, TNF-\u03b1, and IL-1\u03b2) were measured using an ELISA; oxidative stress markers (CSSG, MDA, GSH, and ROS) and the iron ion content via colorimetric assays; mitochondrial morphology by transmission electron microscopy (TEM); and ferroptosis-related proteins (ACSL4, COX2, and GPX4) through Western blotting. Our findings demonstrate that NLRP3-knockout diabetic mice displayed markedly reduced urinary albumin excretion and serum creatinine levels (p &lt; 0.01) compared with wild-type diabetic controls, concurrent with suppressed renal iron overload and ferroptosis, diminished inflammatory cytokine levels, and attenuated oxidative stress. Pathological assessments further revealed ameliorated renal fibrosis and preserved mitochondrial ultrastructure in NLRP3-deficient mice. In vitro, siNLRP3 transfection abrogated high-glucose-induced inflammation, oxidative stress, and ferroptosis in HK-2 cells, effects that were reversed by the ferroptosis inducer erastin (p &lt; 0.01). Mechanistically, NLRP3 deficiency was associated with upregulated GPX4 expression and downregulated ACSL4 and COX2 expression. Collectively, these results indicate that inhibition of the NLRP3 inflammasome mitigates DKD progression by suppressing ferroptosis, underscoring its translational potential as a therapeutic target for this condition.<\/jats:p>","DOI":"10.3390\/ijms27104257","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:49:09Z","timestamp":1778572149000},"page":"4257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["NLRP3 Inflammasome Inhibition Attenuates Diabetic Kidney Injury via the Suppression of Ferroptosis: Mechanistic Insights from In Vivo and In Vitro Models"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5684-4654","authenticated-orcid":false,"given":"Zhili","family":"Tian","sequence":"first","affiliation":[{"name":"The Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"National Clinical Research Center for Geriatrics (WCHSCU), West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghua","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglong","family":"Zhou","sequence":"additional","affiliation":[{"name":"The Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"National Clinical Research Center for Geriatrics (WCHSCU), West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochu","family":"Wu","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Geriatrics (WCHSCU), West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Kidney Research Institute, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"The Center of Gerontology and Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"National Clinical Research Center for Geriatrics (WCHSCU), West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee (2026). 11. 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