{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["71"],"submitter":["Maranon P"],"funding":["Carlos III Health Institute","European Research Council","Spain Ministry of Science and Innovation"],"pubmed_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."],"journal":["Redox biology"],"pagination":["103088"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10902147"],"repository":["biostudies-literature"],"pubmed_title":["Inhibition of ALK3-mediated signalling pathway protects against acetaminophen-induced liver injury."],"pmcid":["PMC10902147"],"pubmed_authors":["Martinez-Ruiz A","Martin MA","Choya-Foces C","Maranon P","Ramos S","Wu H","Rada P","Valverde AM","Rey E","Cubero FJ","Gonzalez-Rodriguez A","Garcia-Monzon C","Isaza SC"],"additional_accession":[]},"is_claimable":false,"name":"Inhibition of ALK3-mediated signalling pathway protects against acetaminophen-induced liver injury.","description":"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.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-28T03:10:09.723Z","creation":"2025-04-04T20:40:00.621Z"},"accession":"S-EPMC10902147","cross_references":{"pubmed":["38401290"],"doi":["10.1016/j.redox.2024.103088"]}}