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dc.contributor.authorSmith, Abigail O
dc.contributor.authorJonassen, Julie A
dc.contributor.authorPreval, Kenley M
dc.contributor.authorDavis, Roger J
dc.contributor.authorPazour, Gregory J
dc.date.accessioned2023-04-25T18:11:48Z
dc.date.available2023-04-25T18:11:48Z
dc.date.issued2021-12-28
dc.identifier.citationSmith AO, Jonassen JA, Preval KM, Davis RJ, Pazour GJ. c-Jun N-terminal kinase (JNK) signaling contributes to cystic burden in polycystic kidney disease. PLoS Genet. 2021 Dec 28;17(12):e1009711. doi: 10.1371/journal.pgen.1009711. PMID: 34962918; PMCID: PMC8746764.en_US
dc.identifier.eissn1553-7404
dc.identifier.doi10.1371/journal.pgen.1009711en_US
dc.identifier.pmid34962918
dc.identifier.urihttp://hdl.handle.net/20.500.14038/51990
dc.description.abstractPolycystic kidney disease is an inherited degenerative disease in which the uriniferous tubules are replaced by expanding fluid-filled cysts that ultimately destroy organ function. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form, afflicting approximately 1 in 1,000 people. It primarily is caused by mutations in the transmembrane proteins polycystin-1 (Pkd1) and polycystin-2 (Pkd2). The most proximal effects of Pkd mutations leading to cyst formation are not known, but pro-proliferative signaling must be involved for the tubule epithelial cells to increase in number over time. The c-Jun N-terminal kinase (JNK) pathway promotes proliferation and is activated in acute and chronic kidney diseases. Using a mouse model of cystic kidney disease caused by Pkd2 loss, we observe JNK activation in cystic kidneys and observe increased nuclear phospho c-Jun in cystic epithelium. Genetic removal of Jnk1 and Jnk2 suppresses the nuclear accumulation of phospho c-Jun, reduces proliferation and reduces the severity of cystic disease. While Jnk1 and Jnk2 are thought to have largely overlapping functions, we find that Jnk1 loss is nearly as effective as the double loss of Jnk1 and Jnk2. Jnk pathway inhibitors are in development for neurodegeneration, cancer, and fibrotic diseases. Our work suggests that the JNK pathway should be explored as a therapeutic target for ADPKD.en_US
dc.language.isoenen_US
dc.relationThis article is based on a previously available preprint in bioRxiv, https://doi.org/10.1101/2021.07.15.452451.
dc.relation.ispartofPLoS Geneticsen_US
dc.relation.urlhttps://doi.org/10.1371/journal.pgen.1009711en_US
dc.rightsCopyright: © 2021 Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.; Attribution 4.0 Internationalen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectKidneysen_US
dc.subjectc-Jun N-terminal kinase signaling cascadeen_US
dc.subjectMouse modelsen_US
dc.subjectFibrosisen_US
dc.subjectWeight lossen_US
dc.subjectPhosphorylationen_US
dc.subjectImmunoblottingen_US
dc.subjectPolycystic kidney diseaseen_US
dc.titlec-Jun N-terminal kinase (JNK) signaling contributes to cystic burden in polycystic kidney diseaseen_US
dc.typeJournal Articleen_US
dc.source.journaltitlePLoS genetics
dc.source.volume17
dc.source.issue12
dc.source.beginpagee1009711
dc.source.endpage
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.identifier.journalPLoS genetics
refterms.dateFOA2023-04-25T18:11:48Z
dc.contributor.departmentMicrobiology and Physiological Systemsen_US
dc.contributor.departmentMorningside Graduate School of Biomedical Sciencesen_US
dc.contributor.departmentProgram in Molecular Medicineen_US
dc.contributor.studentAbigail O. Smith
dc.contributor.studentKenley M. Preval


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Copyright: © 2021 Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.; Attribution 4.0 International
Except where otherwise noted, this item's license is described as Copyright: © 2021 Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.; Attribution 4.0 International