{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T09:50:15Z","timestamp":1768729815335,"version":"3.49.0"},"reference-count":43,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T00:00:00Z","timestamp":1520812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Aux\u00edlio \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["FAPESP grants 14\/23890-4 and 14\/23887-3"],"award-info":[{"award-number":["FAPESP grants 14\/23890-4 and 14\/23887-3"]}]},{"name":"Funda\u00e7\u00e3o de Aux\u00edlio \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["SPEC 13\/50420-6"],"award-info":[{"award-number":["SPEC 13\/50420-6"]}]},{"name":"The European Research Council","award":["ERC Starting Grant 335476"],"award-info":[{"award-number":["ERC Starting Grant 335476"]}]},{"name":"The Fund for Scientific Research-Flanders","award":["FWO grants G009514N and G010214N"],"award-info":[{"award-number":["FWO grants G009514N and G010214N"]}]},{"name":"The University Hospital of the Vrije Universiteit Brussel-Belgium","award":["Willy Gepts Fonds\u201d UZ-VUB"],"award-info":[{"award-number":["Willy Gepts Fonds\u201d UZ-VUB"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although a plethora of signaling pathways are known to drive the activation of hepatic stellate cells in liver fibrosis, the involvement of connexin-based communication in this process remains elusive. Connexin43 expression is enhanced in activated hepatic stellate cells and constitutes the molecular building stone of hemichannels and gap junctions. While gap junctions support intercellular communication, and hence the maintenance of liver homeostasis, hemichannels provide a circuit for extracellular communication and are typically opened by pathological stimuli, such as oxidative stress and inflammation. The present study was set up to investigate the effects of inhibition of connexin43-based hemichannels and gap junctions on liver fibrosis in mice. Liver fibrosis was induced by administration of thioacetamide to Balb\/c mice for eight weeks. Thereafter, mice were treated for two weeks with TAT-Gap19, a specific connexin43 hemichannel inhibitor, or carbenoxolone, a general hemichannel and gap junction inhibitor. Subsequently, histopathological analysis was performed and markers of hepatic damage and functionality, oxidative stress, hepatic stellate cell activation and inflammation were evaluated. Connexin43 hemichannel specificity of TAT-Gap19 was confirmed in vitro by fluorescence recovery after photobleaching analysis and the measurement of extracellular release of adenosine-5\u2032-triphosphate. Upon administration to animals, both TAT-Gap19 and carbenoxolone lowered the degree of liver fibrosis accompanied by superoxide dismutase overactivation and reduced production of inflammatory proteins, respectively. These results support a role of connexin-based signaling in the resolution of liver fibrosis, and simultaneously demonstrate the therapeutic potential of TAT-Gap19 and carbenoxolone in the treatment of this type of chronic liver disease.<\/jats:p>","DOI":"10.3390\/ijms19030817","type":"journal-article","created":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T13:13:48Z","timestamp":1520860428000},"page":"817","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["TAT-Gap19 and Carbenoxolone Alleviate Liver Fibrosis in Mice"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3195-6817","authenticated-orcid":false,"given":"Sara","family":"Crespo Yanguas","sequence":"first","affiliation":[{"name":"Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tereza","family":"Da Silva","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-270, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel","family":"Pereira","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-270, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joost","family":"Willebrords","sequence":"additional","affiliation":[{"name":"Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2178-7589","authenticated-orcid":false,"given":"Micha\u00ebl","family":"Maes","sequence":"additional","affiliation":[{"name":"Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8092-928X","authenticated-orcid":false,"given":"Marina","family":"Sayuri Nogueira","sequence":"additional","affiliation":[{"name":"Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inar","family":"Alves de Castro","sequence":"additional","affiliation":[{"name":"Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Leclercq","sequence":"additional","affiliation":[{"name":"Laboratory of Hepatogastroenterology, Institut de Recherche Exp\u00e9rimentale et clinique, Universit\u00e9 Catholique de Louvain, 1200 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guilherme","family":"Romualdo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Botucatu Medical School, UNESP-S\u00e3o Paulo State University, Botucatu 18600-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2180-1814","authenticated-orcid":false,"given":"Lu\u00eds","family":"Barbisan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Botucatu Medical School, UNESP-S\u00e3o Paulo State University, Botucatu 18600-000, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6452-6982","authenticated-orcid":false,"given":"Luc","family":"Leybaert","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Physiology Group, Ghent University, 9000 Ghent, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruno","family":"Cogliati","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Veterinary Medicine and Animal Science, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-270, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathieu","family":"Vinken","sequence":"additional","affiliation":[{"name":"Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel, 1090 Brussels, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1172\/JCI24282","article-title":"Liver fibrosis","volume":"115","author":"Bataller","year":"2005","journal-title":"J. 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