{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T20:16:09Z","timestamp":1784664969097,"version":"3.55.0"},"reference-count":55,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006692","name":"University of Turin","doi-asserted-by":"publisher","award":["PhD"],"award-info":[{"award-number":["PhD"]}],"id":[{"id":"10.13039\/501100006692","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Unicyte AG","award":["Private funding"],"award-info":[{"award-number":["Private funding"]}]},{"name":"MIUR project &quot;Rita levi Montalcini&quot;","award":["2018-2020"],"award-info":[{"award-number":["2018-2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human liver stem-cell-derived extracellular vesicles (HLSC-EVs) exhibit therapeutic properties in various pre-clinical models of kidney injury. We previously reported an overall improvement in kidney function following treatment with HLSC-EVs in a model of aristolochic acid nephropathy (AAN). Here, we provide evidence that HLSC-EVs exert anti-fibrotic effects by interfering with \u03b2-catenin signalling. A mouse model of AAN and an in vitro pro-fibrotic model were used. The \u03b2-catenin mRNA and protein expression, together with the pro-fibrotic markers \u03b1-SMA and collagen 1, were evaluated in vivo and in vitro following treatment with HLSC-EVs. Expression and functional analysis of miR29b was performed in vitro following HLSC-EV treatments through loss-of-function experiments. Results showed that expression of \u03b2-catenin was amplified both in vivo and in vitro, and \u03b2-catenin gene silencing in fibroblasts prevented AA-induced up-regulation of pro-fibrotic genes, revealing that \u03b2-catenin is an important factor in fibroblast activation. Treatment with HLSC-EVs caused increased expression of miR29b, which was significantly inhibited in the presence of \u03b1-amanitin. The suppression of the miR29b function with a selective inhibitor abolished the anti-fibrotic effects of HLSC-EVs, resulting in the up-regulation of \u03b2-catenin and pro-fibrotic \u03b1-Sma and collagen type 1 genes. Together, these data suggest a novel HLSC-EV-dependent regulatory mechanism in which \u03b2-catenin is down regulated by HLSC-EVs-induced miR29b expression.<\/jats:p>","DOI":"10.3390\/ijms221910780","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T16:23:58Z","timestamp":1633623838000},"page":"10780","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Human Liver Stem Cell Derived Extracellular Vesicles Alleviate Kidney Fibrosis by Interfering with the \u03b2-Catenin Pathway through miR29b"],"prefix":"10.3390","volume":"22","author":[{"given":"Sharad","family":"Kholia","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, University of Torino, 10126 Torino, Italy"},{"name":"Molecular Biotechnology Centre, University of Torino, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Beatriz","family":"Herrera Sanchez","sequence":"additional","affiliation":[{"name":"Molecular Biotechnology Centre, University of Torino, 10126 Torino, Italy"},{"name":"2i3T Societ\u00e0 Per la Gestione Dell\u2019incubatore di Imprese e per il Trasferimento Tecnologico Scarl, University of Torino, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Chiara","family":"Deregibus","sequence":"additional","affiliation":[{"name":"Molecular Biotechnology Centre, University of Torino, 10126 Torino, Italy"},{"name":"2i3T Societ\u00e0 Per la Gestione Dell\u2019incubatore di Imprese e per il Trasferimento Tecnologico Scarl, University of Torino, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8906-0613","authenticated-orcid":false,"given":"Marco","family":"Sasso\u00e8-Pognetto","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, University of Torino, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2795-232X","authenticated-orcid":false,"given":"Giovanni","family":"Camussi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Torino, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0944-6992","authenticated-orcid":false,"given":"Maria Felice","family":"Brizzi","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Torino, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1001\/jama.298.17.2038","article-title":"Prevalence of chronic kidney disease in the United States","volume":"298","author":"Coresh","year":"2007","journal-title":"Jama"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sun, D., Bu, L., Liu, C., Yin, Z., Zhou, X., Li, X., and Xiao, A. 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