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detail.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and Results<\/jats:title><jats:p>Screening of the glycoproteome of urine samples from <jats:styled-content style=\"fixed-case\">ADPKD<\/jats:styled-content> patients revealed that levels of complement factor B (<jats:styled-content style=\"fixed-case\">CFB<\/jats:styled-content>), serpin peptidase inhibitor, complement component 1 inhibitor (<jats:styled-content style=\"fixed-case\">SERPING<\/jats:styled-content>1) and complement component 9 (C9) increased, whereas complement component 1, r subcomponent\u2010like (C1<jats:styled-content style=\"fixed-case\">RL<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>55 and <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>59 levels decreased with disease progression. Immunostaining and Western blot analysis confirmed the enhanced expression of <jats:styled-content style=\"fixed-case\">CFB<\/jats:styled-content> and C9 in cystic kidneys from <jats:styled-content style=\"fixed-case\">ADPKD<\/jats:styled-content> patients. Immunostaining also showed that the expressions of <jats:styled-content style=\"fixed-case\">CFB<\/jats:styled-content> and C9 in renal biopsy tissues from patients with other types of chronic kidney disease were lower than in tissues from <jats:styled-content style=\"fixed-case\">ADPKD<\/jats:styled-content> patients. The effect of the complement inhibitor rosmarinic acid (<jats:styled-content style=\"fixed-case\">RMA<\/jats:styled-content>) was evaluated in <jats:italic>Pkd1<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mice and Han:<jats:styled-content style=\"fixed-case\">SPRD<\/jats:styled-content> Cy\/+ rats. Compared with vehicle\u2010treated <jats:italic>Pkd1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> animals, <jats:styled-content style=\"fixed-case\">RMA<\/jats:styled-content>\u2010treated mice had significantly lower serum creatinine (\u221250%) and blood urea nitrogen (\u221278%) levels, two kidneys\/body weight ratio (\u221260%) and renal cystic index (\u221260%). Similar results were found in Cy\/+ rats. Lower numbers of Ki67\u2010positive nuclei and inflammatory cells and reduced fibrosis were observed in both animal models upon treatment with <jats:styled-content style=\"fixed-case\">RMA<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest that excessive activation of the alternative complement pathway is associated with <jats:styled-content style=\"fixed-case\">ADPKD<\/jats:styled-content> progression, probably mediated by cyst\u2010lining epithelial cell proliferation, tubulointerstitial inflammatory cell infiltration and fibrosis. Targeting the complement system might represent a new therapeutic strategy for <jats:styled-content style=\"fixed-case\">ADPKD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.12214","type":"journal-article","created":{"date-parts":[[2014,2,4]],"date-time":"2014-02-04T23:45:16Z","timestamp":1391557516000},"page":"470-485","source":"Crossref","is-referenced-by-count":45,"title":["Excessive activation of the alternative complement pathway in autosomal dominant polycystic kidney disease"],"prefix":"10.1111","volume":"276","author":[{"given":"Z.","family":"Su","sequence":"first","affiliation":[{"name":"Kidney Institute Department of Nephrology Shanghai Changzheng Hospital Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Wang","sequence":"additional","affiliation":[{"name":"Kidney Institute Department of Nephrology Shanghai Changzheng Hospital Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X.","family":"Gao","sequence":"additional","affiliation":[{"name":"Kidney Institute Department of Nephrology Shanghai Changzheng Hospital Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Physiology University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Pan","sequence":"additional","affiliation":[{"name":"Division of Neuropathology Harborview Medical Center University of Washington School of Medicine Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Hu","sequence":"additional","affiliation":[{"name":"Kidney Institute Department of Nephrology Shanghai Changzheng Hospital Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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