Inhibition of ALK3-mediated signalling pathway protects against acetaminophen-induced liver injury

Simple item page
dc.contributor.authorMarañón, Patricia
dc.contributor.authorWu, Hanghang
dc.contributor.authorCubero Palero, Francisco Javier
dc.contributor.authorValverde, Ángela M.
dc.date.accessioned2024-03-04T09:25:18Z
dc.date.available2024-03-04T09:25:18Z
dc.date.issued2024-02-15
dc.description.abstractAcetaminophen (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.departmentDepto. de Inmunología, Oftalmología y ORL
dc.description.facultyFac. de Medicina
dc.description.refereedTRUE
dc.description.statuspub
dc.identifier.citationMarañón 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.doi10.1016/j.redox.2024.103088
dc.identifier.issn2213-2317
dc.identifier.officialurlhttps://pubmed.ncbi.nlm.nih.gov/38401290/
dc.identifier.relatedurlhttps://pubmed.ncbi.nlm.nih.gov/38401290/
dc.identifier.urihttps://hdl.handle.net/20.500.14352/101884
dc.issue.number71
dc.journal.titleRedox Biology
dc.language.isoeng
dc.page.initial103088
dc.publisherElsevier
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subject.cdu612.017
dc.subject.keywordALK3
dc.subject.keywordAcetaminophen
dc.subject.keywordAcute liver failure
dc.subject.keywordBone morphogenetic proteins
dc.subject.keywordDMH2
dc.subject.keywordDrug induced liver injury
dc.subject.ucmCiencias Biomédicas
dc.subject.ucmInmunología
dc.subject.unesco24 Ciencias de la Vida
dc.subject.unesco2412 Inmunología
dc.titleInhibition of ALK3-mediated signalling pathway protects against acetaminophen-induced liver injury
dc.typejournal article
dc.type.hasVersionVoR
dspace.entity.typePublication
relation.isAuthorOfPublication00cd7853-9957-498a-953b-f38d6cc185a9
relation.isAuthorOfPublicationb3877679-0fbd-42e6-8541-1efeb2df768a
relation.isAuthorOfPublication.latestForDiscovery00cd7853-9957-498a-953b-f38d6cc185a9
Download
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
1-s2.0-S2213231724000648-main.pdf
Size:
11.91 MB
Format:
Adobe Portable Document Format
downoload Download
Collections
Artículos