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During cystogenesis the renal tubules undergo extensive structural alterations that are accompanied by altered cellular signalling, directly and\/or indirectly regulated by the PKD1 and PKD2 proteins. Since transforming growth factor (TGF)\u2010\u03b2 signalling modulates cell proliferation, differentiation, apoptosis, adhesion and migration of various cell types, we studied the activation of this signalling pathway in\n                    <jats:italic>Pkd1<\/jats:italic>\n                    \u2010mutant mouse models at different stages of the disease. Therefore, we analysed expression of the TGF\u03b2\u2013Smad signalling pathway and its target genes in different\n                    <jats:italic>Pkd1<\/jats:italic>\n                    mutant mouse models in various stages of polycystic disease. Nuclear accumulation of P\u2010Smad2 in cyst lining epithelial cells was not observed in the initiation phase but was observed at mild and more advanced stages of PKD. This coincides with mild fibrosis and increased mRNA levels of TGF\u03b2 target genes, such as fibronectin, collagen type I, plasminogen activator inhibitor 1 and matrix metalloproteinase\u20102. At this stage many interstitial fibroblasts were found around cysts, which also showed nuclear localization for P\u2010Smad2. However, bone morphogenetic protein (BMP) signalling, which can antagonize TGF\u03b2 signalling, is not affected, since nuclear expression of P\u2010Smad1\/5\/8 and expression of the BMP target gene, inhibitor of DNA binding\/differential\u20101 (\n                    <jats:italic>ID\u20101<\/jats:italic>\n                    ) is not altered compared to wild\u2010type controls. Also, human kidneys with progressive ADPKD showed increased nuclear localization of P\u2010Smad2, while in general expression of P\u2010Smad1\/5\/8 was weak. These results exclude TGF\u03b2 signalling at the initiation of cystogenesis, but indicate an important role during cyst progression and in fibrogenesis of progressive ADPKD. Copyright \u00a9 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.2734","type":"journal-article","created":{"date-parts":[[2010,5,14]],"date-time":"2010-05-14T10:04:35Z","timestamp":1273831475000},"page":"21-31","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["Elevated TGF\u03b2\u2013Smad signalling in experimental\n                    <i>Pkd1<\/i>\n                    models and human patients with polycystic kidney disease"],"prefix":"10.1002","volume":"222","author":[{"given":"Sabrine","family":"Hassane","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter N","family":"Leonhard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemieke","family":"van der Wal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas 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