Inhibition of ALK3-mediated signalling pathway protects against acetaminophen-induced liver injury
dc.contributor.author | Marañón, Patricia | |
dc.contributor.author | Wu, Hanghang | |
dc.contributor.author | Cubero Palero, Francisco Javier | |
dc.contributor.author | Valverde, Ángela M. | |
dc.date.accessioned | 2024-03-04T09:25:18Z | |
dc.date.available | 2024-03-04T09:25:18Z | |
dc.date.issued | 2024-02-15 | |
dc.description.abstract | Acetaminophen (APAP)-induced liver injury is one of the most prevalent causes of acute liver failure (ALF). We assessed the role of the bone morphogenetic protein (BMP) type I receptors ALK2 and ALK3 in APAP-induced hepatotoxicity. The molecular mechanisms that regulate the balance between cell death and survival and the response to oxidative stress induced by APAP was assessed in cultured human hepatocyte-derived (Huh7) cells treated with pharmacological inhibitors of ALK receptors and with modulated expression of ALK2 or ALK3 by lentiviral infection, and in a mouse model of APAP-induced hepatotoxicity. Inhibition of ALK3 signalling with the pharmacological inhibitor DMH2, or by silencing of ALK3, showed a decreased cell death both by necrosis and apoptosis after APAP treatment. Also, upon APAP challenge, ROS generation was ameliorated and, thus, ROS-mediated JNK and P38 MAPK phosphorylation was reduced in ALK3-inhibited cells compared to control cells. These results were also observed in an experimental model of APAP-induced ALF in which post-treatment with DMH2 after APAP administration significantly reduced liver tissue damage, apoptosis and oxidative stress. This study shows the protective effect of ALK3 receptor inhibition against APAP-induced hepatotoxicity. Furthermore, findings obtained from the animal model suggest that BMP signalling might be a new pharmacological target for the treatment of ALF. | |
dc.description.department | Depto. de Inmunología, Oftalmología y ORL | |
dc.description.faculty | Fac. de Medicina | |
dc.description.refereed | TRUE | |
dc.description.status | pub | |
dc.identifier.citation | Marañón P, Rey E, Isaza SC, Wu H, Rada P, Choya-Foces C, Martínez-Ruiz A, Martín MÁ, Ramos S, García-Monzón C, Cubero FJ, Valverde ÁM, González-Rodríguez Á. Inhibition of ALK3-mediated signalling pathway protects against acetaminophen-induced liver injury. Redox Biol. 2024 Feb 15;71:103088. doi: 10.1016/j.redox.2024.103088. Epub ahead of print. PMID: 38401290; PMCID: PMC10902147. | |
dc.identifier.doi | 10.1016/j.redox.2024.103088 | |
dc.identifier.issn | 2213-2317 | |
dc.identifier.officialurl | https://pubmed.ncbi.nlm.nih.gov/38401290/ | |
dc.identifier.relatedurl | https://pubmed.ncbi.nlm.nih.gov/38401290/ | |
dc.identifier.uri | https://hdl.handle.net/20.500.14352/101884 | |
dc.issue.number | 71 | |
dc.journal.title | Redox Biology | |
dc.language.iso | eng | |
dc.page.initial | 103088 | |
dc.publisher | Elsevier | |
dc.rights | Attribution-NonCommercial 4.0 International | en |
dc.rights.accessRights | open access | |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | |
dc.subject.cdu | 612.017 | |
dc.subject.keyword | ALK3 | |
dc.subject.keyword | Acetaminophen | |
dc.subject.keyword | Acute liver failure | |
dc.subject.keyword | Bone morphogenetic proteins | |
dc.subject.keyword | DMH2 | |
dc.subject.keyword | Drug induced liver injury | |
dc.subject.ucm | Ciencias Biomédicas | |
dc.subject.ucm | Inmunología | |
dc.subject.unesco | 24 Ciencias de la Vida | |
dc.subject.unesco | 2412 Inmunología | |
dc.title | Inhibition of ALK3-mediated signalling pathway protects against acetaminophen-induced liver injury | |
dc.type | journal article | |
dc.type.hasVersion | VoR | |
dspace.entity.type | Publication | |
relation.isAuthorOfPublication | 00cd7853-9957-498a-953b-f38d6cc185a9 | |
relation.isAuthorOfPublication | b3877679-0fbd-42e6-8541-1efeb2df768a | |
relation.isAuthorOfPublication.latestForDiscovery | 00cd7853-9957-498a-953b-f38d6cc185a9 |
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