{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:02:34Z","timestamp":1790521354031,"version":"4.1.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2016,12]]},"abstract":"\n Autosomal dominant polycystic kidney disease (ADPKD), characterized by the formation of numerous kidney cysts, is caused by\n PKD1<\/jats:italic>\n or\n PKD2<\/jats:italic>\n mutations and affects 0.1% of the population. Although recent clinical studies indicate that reduction of cAMP levels slows progression of PKD, this finding has not led to an established safe and effective therapy for patients, indicating the need to find new therapeutic targets. The role of TGF-\n \u03b2<\/jats:italic>\n in PKD is not clearly understood, but nuclear accumulation of phosphorylated SMAD2\/3 in cyst-lining cells suggests the involvement of TGF-\n \u03b2<\/jats:italic>\n signaling in this disease. In this study, we ablated the TGF-\n \u03b2<\/jats:italic>\n type 1 receptor (also termed activin receptor\u2013like kinase 5) in renal epithelial cells of PKD mice, which had little to no effect on the expression of\n SMAD2\/3<\/jats:italic>\n target genes or the progression of PKD. Therefore, we investigated whether alternative TGF-\n \u03b2<\/jats:italic>\n superfamily ligands account for SMAD2\/3 activation in cystic epithelial cells. Activins are members of the TGF-\n \u03b2<\/jats:italic>\n superfamily and drive SMAD2\/3 phosphorylation\n via<\/jats:italic>\n activin receptors, but activins have not been studied in the context of PKD. Mice with PKD had increased expression of activin ligands, even at early stages of disease. In addition, treatment with a soluble activin receptor IIB fusion (sActRIIB-Fc) protein, which acts as a soluble trap to sequester activin ligands, effectively inhibited cyst formation in three distinct mouse models of PKD. These data point to activin signaling as a key pathway in PKD and a promising target for therapy.\n <\/jats:p>","DOI":"10.1681\/asn.2015030287","type":"journal-article","created":{"date-parts":[[2016,3,28]],"date-time":"2016-03-28T21:53:22Z","timestamp":1459202002000},"page":"3589-3599","source":"Crossref","is-referenced-by-count":48,"title":["Inhibition of Activin Signaling Slows Progression of Polycystic Kidney Disease"],"prefix":"10.1681","volume":"27","author":[{"given":"Wouter N.","family":"Leonhard","sequence":"first","affiliation":[{"name":"Human Genetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Kunnen","sequence":"additional","affiliation":[{"name":"Human Genetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna J.","family":"Plugge","sequence":"additional","affiliation":[{"name":"Human 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MOVE Research Institute, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"ten Dijke","sequence":"additional","affiliation":[{"name":"Molecular Cell Biology and Cancer Genomics Centre Netherlands at the Leiden University Medical Center, Leiden, The Netherlands;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn H.","family":"Breuning","sequence":"additional","affiliation":[{"name":"Human Genetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emile","family":"De Heer","sequence":"additional","affiliation":[{"name":"Pathology, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli","family":"Ritvos","sequence":"additional","affiliation":[{"name":"Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Helsinki, Finland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorien 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