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The extent of involvement of TAZ in chronic kidney disease (CKD) is unknown. In our study, increased TAZ nuclear accumulation and expression in the tubulointerstitium was readily evident in 3 models of renal injury including obstructive, aristolochic acid (AA), and diabetic nephropathy, correlating with fibrosis progression. Stable TAZ overexpression in human kidney (HK)\u20102 epithelial cells promoted connective tissue growth factor (CTGF), fibronectin, vimentin, and p21 expression, epithelial dedifferentiation, and growth inhibition, in part,\n                    <jats:italic>via<\/jats:italic>\n                    Sma mothers against decapentaplegic homologue (SMAD)\u20103\u2010dependent CTGF induction. CTGF secretion by TAZ\u2010overexpressing epithelium also triggered proliferative defects in nonengineered HK\u20102 cells confirming a nonautonomous role of TAZ\n                    <jats:italic>(via<\/jats:italic>\n                    a paracrine mechanism) in orchestrating kidney epithelial cell\u2010cell communication. Renal tubular\u2010specific induction of TGF\u2010\u03b21 in mice and TGF\u2010\u03b21 stimulation of HK\u20102 cells resulted in TAZ protein up\u2010regulation. TAZ stable silencing in HK\u20102 cells abrogated TGF\u2010\u03b21\u2013induced expression of target genes without affecting SMAD3 phosphorylation, which is also crucial for fibrotic reprogramming. Thus, TAZ was activated in fibrosis through TGF\u2010\u03b21\u2013dependent mechanisms and sustained TAZ signaling promotes epithelial maladaptive repair. TAZ is also a novel non\u2010SMAD downstream effector of renal TGF\u2010\u03b21 signaling, establishing TAZ as a new antifibrosis target for treatment of CKD.\u2014Anorga, S., Overstreet, J. M., Falke, L. L., Tang, J., Goldschmeding, R. G., Higgins, P. J., Samarakoon, R. Deregulation of Hippo\u2010TAZ pathway during renal injury confers a fibrotic maladaptive phenotype. FASEB J. 32, 2644\u20132657 (2018).\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.201700722r","type":"journal-article","created":{"date-parts":[[2018,1,3]],"date-time":"2018-01-03T10:47:05Z","timestamp":1514976425000},"page":"2644-2657","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["Deregulation of Hippo\u2013TAZ pathway during renal injury confers a fibrotic maladaptive phenotype"],"prefix":"10.1096","volume":"32","author":[{"given":"Sandybell","family":"Anorga","sequence":"first","affiliation":[{"name":"Department of Regenerative and Cancer Cell Biology Albany Medical Center Albany New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Overstreet","sequence":"additional","affiliation":[{"name":"Division of 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