| First Author | Yang B | Year | 2019 |
| Journal | Am J Physiol Renal Physiol | Volume | 317 |
| Issue | 2 | Pages | F221-F228 |
| PubMed ID | 31141402 | Mgi Jnum | J:280969 |
| Mgi Id | MGI:6376344 | Doi | 10.1152/ajprenal.00104.2019 |
| Citation | Yang B, et al. (2019) Interleukin-1 receptor activation aggravates autosomal dominant polycystic kidney disease by modulating regulated necrosis. Am J Physiol Renal Physiol 317(2):F221-F228 |
| abstractText | 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-1alpha and IL-1beta, 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-alpha 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. |
