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Recently, we found serum miRNA-25-3p (miR-25) levels were upregulated in children with Cystic Fibrosis (CF) without liver disease, compared to children with CF-associated liver disease and healthy individuals. Here we examine the role of miR-25 in HSC biology. MiR-25 was detected in the human HSC cell line LX-2 and in primary murine HSCs, and increased with culture-induced activation. Transient overexpression of miR-25 inhibited TGF-\u03b2 and its type 1 receptor (TGFBR1) mRNA expression, TGF-\u03b2-induced Smad2 phosphorylation and subsequent collagen1\u03b11 induction in LX-2 cells. Pull-down experiments with biotinylated miR-25 revealed Notch signaling (co-)activators ADAM-17 and FKBP14 as miR-25 targets in HSCs. NanoString analysis confirmed miR-25 regulation of Notch- and Wnt-signaling pathways. Expression of Notch signaling pathway components and endogenous Notch1 signaling was downregulated in miR-25 overexpressing LX-2 cells, as were components of Wnt signaling such as Wnt5a. We propose that miR-25 acts as a negative feedback anti-fibrotic control during HSC activation by reducing the reactivity of HSCs to TGF-\u03b2-induced collagen expression and modulating the cross-talk between Notch, Wnt and TGF-\u03b2 signaling.<\/jats:p>","DOI":"10.1038\/s41598-019-44865-1","type":"journal-article","created":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T10:03:11Z","timestamp":1560333791000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Overexpression of miRNA-25-3p inhibits Notch1 signaling and TGF-\u03b2-induced collagen expression in hepatic stellate cells"],"prefix":"10.1038","volume":"9","author":[{"given":"Berit","family":"Genz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miranda A.","family":"Coleman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharine M.","family":"Irvine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5410-3636","authenticated-orcid":false,"given":"Jamie R.","family":"Kutasovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariska","family":"Miranda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis D.","family":"Gratte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janina E. 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