{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T02:41:38Z","timestamp":1793932898917,"version":"4.8.0"},"reference-count":27,"publisher":"Portland Press Ltd.","issue":"2","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":19,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,1,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Activation of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3) inflammasome has been reported in diabetic complications including diabetic kidney disease (DKD). However, it remains unknown if NLRP3 inhibition is renoprotective in a clinically relevant interventional approach with established DKD. We therefore examined the effect of the NLRP3-specific inhibitor MCC950 in streptozotocin-induced diabetic mice to measure the impact of NLRP3 inhibition on renal inflammation and associated pathology in DKD. We identified an adverse effect of MCC950 on renal pathology in diabetic animals. Indeed, MCC950-treated diabetic animals showed increased renal inflammation and macrophage infiltration in association with enhanced oxidative stress as well as increased mesangial expansion and glomerulosclerosis when compared with vehicle-treated diabetic animals. Inhibition of the inflammasome by MCC950 in diabetic mice led to renal up-regulation of markers of inflammation (Il1\u03b2, Il18 and Mcp1), fibrosis (Col1, Col4, Fn1, \u03b1-SMA, Ctgf and Tgf\u03b21) and oxidative stress (Nox2, Nox4 and nitrotyrosine). In addition, enhanced glomerular accumulation of pro-inflammatory CD68 positive cells and pro-oxidant factor nitrotyrosine was identified in the MCC950-treated diabetic compared with vehicle-treated diabetic animals. Collectively, in this interventional model of established DKD, NLRP3 inhibition with MCC950 did not show renoprotective effects in diabetic mice. On the contrary, diabetic mice treated with MCC950 exhibited adverse renal effects particularly enhanced renal inflammation and injury including mesangial expansion and glomerulosclerosis.<\/jats:p>","DOI":"10.1042\/cs20210865","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T04:25:42Z","timestamp":1642652742000},"page":"167-180","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Adverse renal effects of NLRP3 inflammasome inhibition by MCC950 in an interventional model of diabetic kidney disease"],"prefix":"10.1042","volume":"136","author":[{"given":"Jakob\u00a0A.","family":"\u00d8stergaard","sequence":"first","affiliation":[{"name":"Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia"},{"name":"Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark"},{"name":"Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay\u00a0C.","family":"Jha","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arpeeta","family":"Sharma","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Oxidative Stress Laboratory, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aozhi","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy\u00a0S.Y.","family":"Choi","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Oxidative Stress Laboratory, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy\u00a0B.","family":"de Haan","sequence":"additional","affiliation":[{"name":"Baker Heart and Diabetes Institute, Oxidative Stress Laboratory, Melbourne, Victoria, Australia"},{"name":"Department of Immunology and Pathology, Central Clinical School, Monash University, Melbourne, Victoria, Australia"},{"name":"Department of Cardiometabolic Health, Melbourne University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark\u00a0E.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia"},{"name":"Baker Heart and Diabetes Institute, Oxidative Stress Laboratory, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2192-5822","authenticated-orcid":false,"given":"Karin","family":"Jandeleit-Dahm","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia"},{"name":"German Diabetes Centre, Leibniz Centre for Diabetes Research at the Heinrich Heine University, Duesseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"2022012009252309600_B1","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1007\/s40620-020-00749-6","article-title":"Targeting oxidative stress and anti-oxidant defence in diabetic kidney disease","volume":"33","author":"\u00d8stergaard","year":"2020","journal-title":"J. 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