{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:32:14Z","timestamp":1761093134022,"version":"build-2065373602"},"reference-count":79,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,6,17]],"date-time":"2019-06-17T00:00:00Z","timestamp":1560729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002997","name":"Nierstichting","doi-asserted-by":"publisher","award":["CP10.12\u2010DIPAK"],"award-info":[{"award-number":["CP10.12\u2010DIPAK"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Autosomal Dominant Polycystic Kidney Disease is characterised by the development of fluid\u2010filled cysts in the kidneys which lead to end\u2010stage renal disease (ESRD). In the majority of cases, the disease is caused by a mutation in the <jats:italic>Pkd1<\/jats:italic> gene. In a previous study, we demonstrated that renal injury can accelerate cyst formation in <jats:italic>Pkd1<\/jats:italic> knock\u2010out (KO) mice. In that study, we found that after injury four\u2010jointed (Fjx1), an upstream regulator of planar cell polarity and the Hippo pathway, was aberrantly expressed in <jats:italic>Pkd1<\/jats:italic> KO mice compared to WT. Therefore, we hypothesised a role for Fjx1 in injury\/repair and cyst formation. We generated single and double deletion mice for <jats:italic>Pkd1<\/jats:italic> and <jats:italic>Fjx1<\/jats:italic>, and we induced toxic renal injury using the nephrotoxic compound 1,2\u2010dichlorovinyl\u2010cysteine. We confirmed that nephrotoxic injury can accelerate cyst formation in <jats:italic>Pkd1<\/jats:italic> mutant mice. This caused <jats:italic>Pkd1<\/jats:italic> KO mice to reach ESRD significantly faster; unexpectedly, double KO mice survived significantly longer. Cyst formation was comparable in both models, but we found significantly less fibrosis and macrophage infiltration in double KO mice. Taken together, these data suggest that <jats:italic>Fjx1<\/jats:italic> disruption protects the cystic kidneys against kidney failure by reducing inflammation and fibrosis. Moreover, we describe, for the first time, an interesting (yet unidentified) mechanism that partially discriminates cyst growth from fibrogenesis. \u00a9 2019 The Authors. <jats:italic>The Journal of Pathology<\/jats:italic> published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.5286","type":"journal-article","created":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T23:17:02Z","timestamp":1556666222000},"page":"114-125","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Four\u2010jointed knock\u2010out delays renal failure in an ADPKD model with kidney injury"],"prefix":"10.1002","volume":"249","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3263-3158","authenticated-orcid":false,"given":"Chiara","family":"Formica","sequence":"first","affiliation":[{"name":"Department of Human Genetics Leiden University Medical Center  Leiden The 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