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Results of clinical studies testing RAS inhibitors in slowing the progression of cystic disease in ADPKD are inconclusive, and we hypothesized that current RAS inhibitors do not adequately suppress intrarenal RAS. For this study, we compared a novel Gen 2 antisense oligonucleotide (ASO) that inhibits angiotensinogen (Agt) synthesis to lisinopril in adult conditional\n                    <jats:italic>Pkd1<\/jats:italic>\n                    systemic\u2010knockout mice, a model of ADPKD. Six weeks after\n                    <jats:italic>Pkd1<\/jats:italic>\n                    global gene knockout, the mice were treated with Agt\u2010ASO (66 mg\/kg\/wk), lisinopril (100 mg\/kg\/d), PBS (control), or scrambled ASO (66 mg\/kg\/wk) for 10 wk, followed by tissue collection. Agt ASO resulted in significant reduction in plasma, liver, and kidney Agt, and increased kidney renin compared with control treatments. Kidneys from Agt\u2010ASO\u2010treated mice were not as enlarged and showed reduced cystic volume compared with lisinopril or control treatments. Blood pressure was better controlled with lisinopril than with Agt\u2010ASO. Agt\u2010ASO suppressed cell proliferation in both cystic and noncystic cells compared with lisinopril and control treatments. However, Agt\u2010ASO did not reduce cell proliferation in liver, which indicates that Agt\u2010ASO targets cell signaling pathways that specifically suppresses cystogenesis in the kidney. These data suggest that Agt\u2010ASO effectively attenuates intrarenal RAS and therefore can be a novel and effective agent for treating ADPKD.\u2014Saigusa, T., Dang, Y., Mullick, A.E., Yeh, S.T., Zile, M.R., Baicu, C. F., Bell, P. D. Suppressing angiotensinogen synthesis attenuates kidney cyst formation in a\n                    <jats:italic>Pkd1<\/jats:italic>\n                    mouse model.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    30, 370\u2010379 (2016).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.15-279299","type":"journal-article","created":{"date-parts":[[2015,9,21]],"date-time":"2015-09-21T23:08:10Z","timestamp":1442876890000},"page":"370-379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Suppressing angiotensinogen synthesis attenuates kidney cyst formation in a\n                    <i>Pkd1<\/i>\n                    mouse model"],"prefix":"10.1096","volume":"30","author":[{"given":"Takamitsu","family":"Saigusa","sequence":"first","affiliation":[{"name":"Division of Nephrology Medical University of South Carolina Charleston South Carolina USA"},{"name":"Ralph Johnson Veterans Affairs Medical Center Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujing","family":"Dang","sequence":"additional","affiliation":[{"name":"Division of Nephrology Medical University of South Carolina Charleston South Carolina USA"},{"name":"Ralph Johnson Veterans Affairs Medical Center Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam E.","family":"Mullick","sequence":"additional","affiliation":[{"name":"Isis Pharmaceuticals Carlsbad California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve T.","family":"Yeh","sequence":"additional","affiliation":[{"name":"Isis Pharmaceuticals Carlsbad California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Zile","sequence":"additional","affiliation":[{"name":"Division of Cardiology Medical University of South Carolina Charleston South Carolina USA"},{"name":"Ralph Johnson Veterans Affairs Medical Center Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalin F.","family":"Baicu","sequence":"additional","affiliation":[{"name":"Division of Cardiology Medical University of South Carolina Charleston South Carolina USA"},{"name":"Ralph Johnson Veterans Affairs Medical Center Charleston South Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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