{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:39:51Z","timestamp":1791297591108,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,3,7]],"date-time":"2011-03-07T00:00:00Z","timestamp":1299456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002997","name":"Dutch Kidney Foundation","doi-asserted-by":"crossref","award":["NSN C05-2132"],"award-info":[{"award-number":["NSN C05-2132"]}],"id":[{"id":"10.13039\/501100002997","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Polycystic Kidney Disease Research Foundation","award":["175G08a"],"award-info":[{"award-number":["175G08a"]}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2011,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive deterioration of renal function and formation of cysts, and is an important cause of end\u2010stage renal disease. Previously we showed that tubular epithelial injury accelerates cyst formation in inducible\n                    <jats:italic>Pkd1<\/jats:italic>\n                    \u2010deletion mice. In these mice, expression of the planar cell polarity (PCP) component Four\u2010jointed (\n                    <jats:italic>Fjx1<\/jats:italic>\n                    ) is decreased during epithelial repair, while in control mice\n                    <jats:italic>Fjx1<\/jats:italic>\n                    expression is increased and may be required during tissue regeneration. In cystic kidneys, however,\n                    <jats:italic>Fjx1<\/jats:italic>\n                    expression is also increased. Besides a PCP component, Four\u2010jointed is also implicated in the Hippo\u2010signalling pathway. This pathway is involved in organ size control by regulating proliferation and apoptosis. The role of Hippo signalling, together with the opposing expression pattern of\n                    <jats:italic>Fjx1<\/jats:italic>\n                    during epithelial repair and at cystic stages, triggered us to investigate the activity of the Hippo pathway during these processes. Therefore, we examined its final effector molecule, the transcriptional co\u2010activator Yes\u2010associated protein (YAP) and observed that during tissue repair, YAP expression was not different between\n                    <jats:italic>Pkd1<\/jats:italic>\n                    \u2010deletion mice and controls, ie during tissue regeneration YAP expression was increased and predominantly localized in the cytoplasm but normalized after tissue repair. At a later stage, however, in cystic epithelia and epithelia of dilated tubules, strong nuclear YAP accumulation was observed, accompanied by up\u2010regulation of the YAP transcriptional targets\n                    <jats:italic>Birc\u20103, Ctgf, InhbA<\/jats:italic>\n                    , and\n                    <jats:italic>Fjx1<\/jats:italic>\n                    . Altered activity of the Hippo pathway was confirmed in renal tissues from human ADPKD and ARPKD patients, as well as in cystic renal tumours. Our data strengthen the concept that during epithelial repair Four\u2010jointed is involved in PCP signalling, while in cystic kidneys it is related to Hippo signalling and cyst growth. Copyright \u00a9 2011 Pathological Society of Great Britain and Ireland. 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