{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:10:56Z","timestamp":1791443456924,"version":"4.3.3"},"reference-count":42,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","doi-asserted-by":"publisher","award":["DK118019"],"award-info":[{"award-number":["DK118019"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000850","name":"National Heart and Lung Institute (NHLI)","doi-asserted-by":"publisher","award":["HL128355"],"award-info":[{"award-number":["HL128355"]}],"id":[{"id":"10.13039\/501100000850","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs (VA)","doi-asserted-by":"publisher","award":["BX000893"],"award-info":[{"award-number":["BX000893"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2019,8,1]]},"abstract":"<jats:p> Autosomal dominant polycystic kidney disease (ADPKD) is associated with increased chemokines, cytokines, and growth factors in the diseased kidney. We found that both isoforms of IL-1, IL-1\u03b1 and IL-1\u03b2, were upregulated in ADPKD tissues. Here, we used a unique murine ADPKD model with selective deletion of polycystin-1 ( pkd1) in the kidney (KPKD1) to study the role of IL-1 signaling in ADPKD progression. In KPKD mice, genetic deletion of the IL-1 receptor [IL-1 receptor (IL-1R) knockout (KO)] prolongs survival and attenuates cyst volume. Compared with IL-1R wild-type KPKD1 kidneys, IL-1R KO KPKD1 kidneys have upregulated TNF-\u03b1 gene expression, with consequent elevations in markers for TNF-dependent regulated necrosis. We further observed that regulated necrosis was increased in ADPKD tissues from both humans and mice. To confirm that enhanced necroptosis is protective in ADPKD, we treated KPKD1 mice with an inhibitor of regulated necrosis (Nec-1). Regulated necrosis suppression augments kidney weights, suggesting that regulated necrosis is required to limit kidney growth in ADPKD. Thus, IL-1R activation drives ADPKD progression by paradoxically limiting regulated necrosis. <\/jats:p>","DOI":"10.1152\/ajprenal.00104.2019","type":"journal-article","created":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T15:01:41Z","timestamp":1559142101000},"page":"F221-F228","source":"Crossref","is-referenced-by-count":29,"title":["Interleukin-1 receptor activation aggravates autosomal dominant polycystic kidney disease by modulating regulated necrosis"],"prefix":"10.1152","volume":"317","author":[{"given":"Bo","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Nephrology, Kidney Institution of Chinese People\u2019s Liberation Army, Changzheng Hospital, Shanghai, China"},{"name":"Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Fu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Kidney 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