{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:03:57Z","timestamp":1790615037886,"version":"4.1.0"},"reference-count":45,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK081579"],"award-info":[{"award-number":["R01DK081579"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30DK106912"],"award-info":[{"award-number":["P30DK106912"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001296","name":"PKD Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001296","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:p> Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the presence of numerous fluid-filled cysts, extensive fibrosis, and the progressive decline in kidney function. Transforming growth factor-\u03b21 (TGF-\u03b21), an important mediator for renal fibrosis and chronic kidney disease, is overexpressed by cystic cells compared with normal kidney cells; however, its role in PKD pathogenesis remains undefined. To investigate the effect of TGF-\u03b21 on cyst growth, fibrosis, and disease progression, we overexpressed active TGF-\u03b21 specifically in collecting ducts (CDs) of phenotypic normal ( Pkd1<jats:sup>RC\/+<\/jats:sup>) and Pkd1<jats:sup>RC\/RC<\/jats:sup> mice. In normal mice, CD-specific TGF-\u03b21 overexpression caused tubule dilations by 5 wk of age that were accompanied by increased levels of phosphorylated SMAD3, \u03b1-smooth muscle actin, vimentin, and periostin; however, it did not induce overt cyst formation by 20 wk. In Pkd1<jats:sup>RC\/RC<\/jats:sup> mice, CD overexpression of TGF-\u03b21 increased cyst epithelial cell proliferation. However, extensive fibrosis limited cyst enlargement and caused contraction of the kidneys, leading to a loss of renal function and a shortened lifespan of the mice. These data demonstrate that TGF-\u03b21-induced fibrosis constrains cyst growth and kidney enlargement and accelerates the decline of renal function, supporting the hypothesis that a combined therapy that inhibits renal cyst growth and fibrosis will be required to effectively treat ADPKD. <\/jats:p>","DOI":"10.1152\/ajprenal.00366.2020","type":"journal-article","created":{"date-parts":[[2020,11,9]],"date-time":"2020-11-09T19:21:42Z","timestamp":1604949702000},"page":"F1135-F1148","source":"Crossref","is-referenced-by-count":42,"title":["Overexpression of TGF-\u03b21 induces renal fibrosis and accelerates the decline in kidney function in polycystic kidney disease"],"prefix":"10.1152","volume":"319","author":[{"given":"Yan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas"},{"name":"Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, 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