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Few effective therapeutic options are available to prevent the progression of IF\/TA. We applied a meta-analysis approach on IF\/TA molecular datasets in Gene Expression Omnibus to identify a robust 85-gene signature, which was used for computational drug repurposing analysis. Among the top ranked compounds predicted to be therapeutic for IF\/TA were azathioprine, a drug to prevent acute rejection in renal transplantation, and kaempferol and esculetin, two drugs not previously described to have efficacy for IF\/TA. We experimentally validated the anti-fibrosis effects of kaempferol and esculetin using renal tubular cells<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>in a mouse Unilateral Ureteric Obstruction (UUO) model. Kaempferol significantly attenuated TGF-\u03b21-mediated profibrotic pathways<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>, while esculetin significantly inhibited Wnt\/\u03b2-catenin pathway<jats:italic>in vitro and in vivo<\/jats:italic>. Histology confirmed significantly abrogated fibrosis by kaempferol and esculetin<jats:italic>in vivo<\/jats:italic>. We developed an integrative computational framework to identify kaempferol and esculetin as putatively novel therapies for IF\/TA and provided experimental evidence for their therapeutic activities<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>using preclinical models. The findings suggest that both drugs might serve as therapeutic options for IF\/TA.<\/jats:p>","DOI":"10.1038\/srep39487","type":"journal-article","created":{"date-parts":[[2017,1,4]],"date-time":"2017-01-04T10:11:31Z","timestamp":1483524691000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Novel Therapeutics Identification for Fibrosis in Renal Allograft Using Integrative Informatics Approach"],"prefix":"10.1038","volume":"7","author":[{"given":"Li","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilana","family":"Greene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Readhead","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madhav C.","family":"Menon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian A.","family":"Kidd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew V.","family":"Uzilov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengguo","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nimrod","family":"Philippe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Schroppel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John Cijiang","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel T.","family":"Dudley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,1,4]]},"reference":[{"key":"BFsrep39487_CR1","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1111\/j.1600-6143.2004.00515.x","volume":"4","author":"HU Meier-Kriesche","year":"2004","unstructured":"Meier-Kriesche, H. 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