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The\n                    <jats:italic>PKD1<\/jats:italic>\n                    gene product is a Wnt cell-surface receptor. We previously showed that a lack of the\n                    <jats:italic>PKD2<\/jats:italic>\n                    gene product, PC2, increases \u03b2-catenin signaling in mouse embryonic fibroblasts, kidney renal epithelia, and isolated renal collecting duct cells. However, it remains unclear whether \u03b2-catenin signaling plays a role in polycystic kidney disease phenotypes or if a Wnt inhibitor can halt cyst formation in ADPKD disease models. Here, using genetic and pharmacologic approaches, we demonstrated that the elevated \u03b2-catenin signaling caused by PC2 deficiency contributes significantly to disease phenotypes in a mouse ortholog of human ADPKD. Pharmacologically inhibiting \u03b2-catenin stability or the production of mature Wnt protein, or genetically reducing the expression of\n                    <jats:italic>Ctnnb1<\/jats:italic>\n                    (which encodes \u03b2-catenin), suppressed the formation of renal cysts, improved renal function, and extended survival in ADPKD mice. Our study clearly demonstrates the importance of \u03b2-catenin signaling in disease phenotypes associated with\n                    <jats:italic>Pkd2<\/jats:italic>\n                    mutation. It also describes the effects of two Wnt inhibitors, XAV939 and LGK974, on various Wnt signaling targets as a potential therapeutic modality for ADPKD, for which there is currently no effective therapy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.95874","type":"journal-article","created":{"date-parts":[[2018,3,7]],"date-time":"2018-03-07T11:02:53Z","timestamp":1520420573000},"source":"Crossref","is-referenced-by-count":44,"title":["Canonical Wnt inhibitors ameliorate cystogenesis in a mouse ortholog of human ADPKD"],"prefix":"10.1172","volume":"3","author":[{"given":"Ao","family":"Li","sequence":"first","affiliation":[{"name":"Anhui Province PKD Center, Institute and Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China."},{"name":"Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Xu","sequence":"additional","affiliation":[{"name":"Anhui Province PKD Center, Institute and Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Fan","sequence":"additional","affiliation":[{"name":"Anhui Province PKD Center, Institute and Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Meng","sequence":"additional","affiliation":[{"name":"Anhui Province PKD Center, Institute and Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xufeng","family":"Shen","sequence":"additional","affiliation":[{"name":"Anhui Province PKD Center, Institute and Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Anhui Province PKD Center, Institute and 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China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaozhao","family":"Liang","sequence":"additional","affiliation":[{"name":"Anhui Province PKD Center, Institute and Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianqing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, 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