{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T22:01:27Z","timestamp":1768773687037,"version":"3.49.0"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,4,23]],"date-time":"2016-04-23T00:00:00Z","timestamp":1461369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2016,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Renal dysplasia, the leading cause of renal failure in children, is characterized by disrupted branching of the collecting ducts and primitive tubules, with an expansion of the stroma, yet a role for the renal stroma in the genesis of renal dysplasia is not known. Here, we demonstrate that expression of \u03b2\u2010catenin, a key transcriptional co\u2010activator in renal development, is markedly increased in the expanded stroma in human dysplastic tissue. To understand its contribution to the genesis of renal dysplasia, we generated a mouse model that overexpresses \u03b2\u2010catenin specifically in stromal progenitors, termed <jats:italic>\u03b2\u2010cat<jats:sup>GOF\u2010S<\/jats:sup><\/jats:italic>. Histopathological analysis of <jats:italic>\u03b2\u2010cat<jats:sup>GOF<\/jats:sup><jats:sup>\u2010S<\/jats:sup><\/jats:italic> mice revealed a marked expansion of fibroblast cells surrounding primitive ducts and tubules, similar to defects observed in human dysplastic kidneys. Characterization of the renal stroma in <jats:italic>\u03b2\u2010cat<jats:sup>GOF<\/jats:sup><jats:sup>\u2010S<\/jats:sup><\/jats:italic> mice revealed altered stromal cell differentiation in the expanded renal stroma demonstrating that this is not renal stroma but instead a population of stroma\u2010like cells. These cells overexpress ectopic Wnt4 and Bmp4, factors necessary for endothelial cell migration and blood vessel formation. Characterization of the renal vasculature demonstrated disrupted endothelial cell migration, organization, and vascular morphogenesis in <jats:italic>\u03b2\u2010cat<jats:sup>GOF<\/jats:sup><jats:sup>\u2010S<\/jats:sup><\/jats:italic> mice. Analysis of human dysplastic tissue demonstrated a remarkably similar phenotype to that observed in our mouse model, including altered stromal cell differentiation, ectopic Wnt4 expression in the stroma\u2010like cells, and disrupted endothelial cell migration and vessel formation. Our findings demonstrate that the overexpression of \u03b2\u2010catenin in stromal cells is sufficient to cause renal dysplasia. Further, the pathogenesis of renal dysplasia is one of disrupted stromal differentiation and vascular morphogenesis. Taken together, this study demonstrates for the first time the contribution of stromal \u03b2\u2010catenin overexpression to the genesis of renal dysplasia. Copyright \u00a9 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/path.4713","type":"journal-article","created":{"date-parts":[[2016,3,9]],"date-time":"2016-03-09T04:06:45Z","timestamp":1457496405000},"page":"174-185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Stromal \u03b2\u2010catenin overexpression contributes to the pathogenesis of renal dysplasia"],"prefix":"10.1002","volume":"239","author":[{"given":"Felix J","family":"Boivin","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University  Hamilton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Sarin","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University  Hamilton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pari","family":"Dabas","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University  Hamilton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Karolak","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Maine Medical Center Research Institute  Scarborough Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leif","family":"Oxburgh","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine Maine Medical Center Research Institute  Scarborough Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darren","family":"Bridgewater","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Medicine McMaster University  Hamilton Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,4,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2007.10.009"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-002-0928-9"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-007-0479-1"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.1999.560502.x"},{"key":"e_1_2_6_6_1","unstructured":"RosenblumND.Overview of congenital anomalies of the kidney and urinary tract (CAKUT) 2012. 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