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University","doi-asserted-by":"publisher","award":["2020zzts869"],"award-info":[{"award-number":["2020zzts869"]}],"id":[{"id":"10.13039\/501100012476","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is a vital component of many inflammatory responses. Here, we intended to investigate the involvement of NLRP3 in lipopolysaccharide (LPS)-induced sepsis-associated acute kidney injury (S-AKI) and explore its mechanisms. For the first time, we validated elevated NLRP3 expression in the renal tissues of S-AKI patients by immunohistochemistry analysis. Through LPS injection in both wild-type and Nlrp3\u2212\/\u2212 mice, a S-AKI model was developed. It was found that LPS-induced kidney injury, including an abnormal morphology in a histological examination, abnormal renal function in a laboratory examination, and an increase in the expression of AKI biomarkers, was dramatically reversed in Nlrp3-deficient mice. Nlrp3 deletion alleviated renal inflammation, as evidenced by the suppression of the expression of pro-inflammatory cytokines and chemokines. A combinative analysis of RNA sequencing and the FerrDb V2 database showed that Nlrp3 knockout regulated multiple metabolism pathways and ferroptosis in LPS-induced S-AKI. Further qPCR coupled with Prussian blue staining demonstrated that Nlrp3 knockout inhibited murine renal ferroptosis, indicating a novel mechanism involving S-AKI pathogenesis by NLRP3. Altogether, the aforementioned findings suggest that Nlrp3 deficiency alleviates LPS-induced S-AKI by reducing renal inflammation and ferroptosis. Our data highlight that NLRP3 is a potential therapeutic target for S-AKI.<\/jats:p>","DOI":"10.3390\/biology12091188","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T11:31:18Z","timestamp":1693481478000},"page":"1188","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Nlrp3 Deficiency Alleviates Lipopolysaccharide-Induced Acute Kidney Injury via Suppressing Renal Inflammation and Ferroptosis in Mice"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0672-2613","authenticated-orcid":false,"given":"Zhilan","family":"Li","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5711-1367","authenticated-orcid":false,"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongling","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenyi","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou 412007, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6977-0183","authenticated-orcid":false,"given":"Weiru","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of General Medicine, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1565-327X","authenticated-orcid":false,"given":"Xin","family":"Ni","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China"},{"name":"International Collaborative Research Center for Medical Metabolomics, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1007\/s00134-015-3934-7","article-title":"Epidemiology of acute kidney injury in critically ill patients: The multinational AKI-EPI study","volume":"41","author":"Hoste","year":"2015","journal-title":"Intensive Care Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1007\/s00134-008-1367-2","article-title":"Acute kidney injury in septic shock: Clinical outcomes and impact of duration of hypotension prior to initiation of antimicrobial therapy","volume":"35","author":"Bagshaw","year":"2009","journal-title":"Intensive Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1164\/rccm.201505-0995OC","article-title":"The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock","volume":"193","author":"Kellum","year":"2016","journal-title":"Am. 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