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Título: | ACBP/DBI protein neutralization confers autophagy-dependent organ protection through inhibition of cell loss, inflammation, and fibrosis |
Autor: | Motiño, Omar CSIC ORCID CVN; Lambertucci, Flavia; Anagnostopoulos, Gerasimos; Li, Sijing; Nah, Jihoon; Castoldi, Francesca; Senovilla, Laura CSIC ORCID CVN; Montégut, Léa; Chen, Hui; Durand, Sylvére; Bourgin, Mélanie; Aprahamian, Fanny; Nirmalathasan, Nitharsshini; Álvarez-Valadez, Karla; Sauvat, Allan; Carbonnier, Vincent; Djavaheri-Mergny, Mojgan; Pietrocola, Federico; Sadoshima, Junichi; Chiara Maiur, María; Martins, Isabelle; Kroemer, Guido | Palabras clave: | Acyl-CoA binding protein Autophagy Non-alcoholic steatohepatitis Myocardium infarction Fibrosis |
Fecha de publicación: | 3-oct-2022 | Editor: | National Academy of Sciences (U.S.) | Citación: | Proceedings of the National Academy of Sciences of the United States of America 119(41): e2207344119 (2022) | Resumen: | Acyl-coenzyme A (CoA)–binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is an extracellular feedback regulator of autophagy. Here, we report that injection of a monoclonal antibody neutralizing ACBP/DBI (α-DBI) protects the murine liver against ischemia/reperfusion damage, intoxication by acetaminophen and concanavalin A, and nonalcoholic steatohepatitis caused by methionine/choline-deficient diet as well as against liver fibrosis induced by bile duct ligation or carbon tetrachloride. α-DBI downregulated proinflammatory and profibrotic genes and upregulated antioxidant defenses and fatty acid oxidation in the liver. The hepatoprotective effects of α-DBI were mimicked by the induction of ACBP/DBI-specific autoantibodies, an inducible Acbp/Dbi knockout or a constitutive Gabrg2F77I mutation that abolishes ACBP/DBI binding to the GABAA receptor. Liver-protective α-DBI effects were lost when autophagy was pharmacologically blocked or genetically inhibited by knockout of Atg4b. Of note, α-DBI also reduced myocardium infarction and lung fibrosis, supporting the contention that it mediates broad organ-protective effects against multiple insults. | Versión del editor: | http://dx.doi.org/10.1073/pnas.2207344119 | URI: | http://hdl.handle.net/10261/296251 | DOI: | 10.1073/pnas.2207344119 | Identificadores: | doi: 10.1073/pnas.2207344119 issn: 0027-8424 e-issn: 1091-6490 |
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ACBP_DBI protein neutralization_Motiño_PV_Art2022.pdf | 4,63 MB | Adobe PDF | Visualizar/Abrir |
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