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Previously, we showed that periostin, a matricellular protein involved in tissue repair, is overexpressed by cystic epithelial cells of PKD kidneys. Periostin binds \u03b1<jats:sub>V<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>-integrins and activates integrin-linked kinase (ILK), leading to Akt\/mammalian target of rapamycin (mTOR)-mediated proliferation of human PKD cells. By contrast, periostin does not stimulate the proliferation of normal human kidney cells. This difference in the response to periostin is due to elevated expression of \u03b1<jats:sub>V<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>-integrins by cystic cells. To determine whether periostin accelerates cyst growth and fibrosis, we generated mice with conditional overexpression of periostin in the collecting ducts (CDs). Ectopic CD expression of periostin was not sufficient to induce cyst formation or fibrosis in wild-type mice. However, periostin overexpression in pcy\/pcy ( pcy) kidneys significantly increased mTOR activity, cell proliferation, cyst growth, and interstitial fibrosis; and accelerated the decline in renal function. Moreover, CD-specific overexpression of periostin caused a decrease in the survival of pcy mice. These pathological changes were accompanied by increased renal expression of vimentin, \u03b1-smooth muscle actin, and type I collagen. We also found that periostin increased gene expression of pathways involved in repair, including integrin and growth factor signaling and ECM production, and it stimulated focal adhesion kinase, Rho GTPase, cytoskeletal reorganization, and migration of PKD cells. These results suggest that periostin stimulates signaling pathways involved in an abnormal tissue repair process that contributes to cyst growth and fibrosis in PKD. <\/jats:p>","DOI":"10.1152\/ajprenal.00246.2018","type":"journal-article","created":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T15:14:44Z","timestamp":1539789284000},"page":"F1695-F1707","source":"Crossref","is-referenced-by-count":32,"title":["Periostin overexpression in collecting ducts accelerates renal cyst growth and fibrosis in polycystic kidney disease"],"prefix":"10.1152","volume":"315","author":[{"given":"Archana","family":"Raman","sequence":"first","affiliation":[{"name":"The Jared Grantham Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas"},{"name":"Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen 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