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OPN expression is markedly increased in cystic epithelial cells of polycystic kidney disease (PKD) kidneys; however, its role in PKD progression remains unclear. We investigated the in\u00a0vitro effects of recombinant OPN on the proliferation of tubular epithelial cells from PKD and normal human kidneys and in\u00a0vivo effects of OPN deletion on kidney cyst formation, fibrosis, and mineral metabolism in <jats:italic>pcy\/pcy<\/jats:italic> mice, a non\u2010orthologous model of autosomal\u2010dominant PKD. In\u00a0vitro studies revealed that OPN enhanced the proliferation of PKD cells but had no effect on normal kidney cells. Deletion of OPN in <jats:italic>pcy\/pcy<\/jats:italic> mice significantly reduced kidney cyst burden; however, this was accompanied by increased fibrosis and no change in kidney function. The loss of OPN had no effect on kidney macrophage numbers, cyst epithelial cell proliferation, or apoptosis. Furthermore, there was no difference in kidney mineral deposition or mineral metabolism parameters between <jats:italic>pcy\/pcy<\/jats:italic> mice with and without OPN expression. Global deletion of OPN reduced kidney cyst burden, while paradoxically exacerbating kidney fibrosis in mice with cystic kidney disease.<\/jats:p>","DOI":"10.14814\/phy2.70038","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T03:40:36Z","timestamp":1725594036000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Osteopontin deletion attenuates cyst growth but exacerbates fibrosis in mice with cystic kidney disease"],"prefix":"10.14814","volume":"12","author":[{"given":"Kyle P.","family":"Jansson","sequence":"first","affiliation":[{"name":"The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Kuluva","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Swanson","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1798-8046","authenticated-orcid":false,"given":"Kurt A.","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine University of Oklahoma Health Sciences Center  Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A.","family":"Fields","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Pathology and Laboratory Medicine University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren P.","family":"Wallace","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Rowe","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4580-5745","authenticated-orcid":false,"given":"Jason R.","family":"Stubbs","sequence":"additional","affiliation":[{"name":"The Jared Grantham Kidney Institute University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Division of Nephrology and Hypertension, Department of Internal Medicine University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.09.022"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109014"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00065.x"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lungcan.2007.03.019"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI12980"},{"key":"e_1_2_10_7_1","first-page":"353","article-title":"Evidence for a role of osteopontin in macrophage infiltration in response to pathological stimuli in\u00a0vivo","volume":"152","author":"Giachelli C. 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