ACBP/DBI protein neutralization confers autophagy-dependent organ protection through inhibition of cell loss, inflammation, and fibrosis

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, into...

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Detalles Bibliográficos
Autores: Motiño, Omar, Lambertucci, Flavia, Anagnostopoulos, Gerasimos, Li, Sijing, Nah, Jihoon, Castoldi, Francesca, Senovilla, Laura, Montégut, Léa, Chen, Hui, Durand, Sylvère, Bourgin, Mélanie, Aprahamian, Fanny, Nirmalathasan, Nitharsshini, Álvarez-Valadez, Karla, Sauvat, Allan, Carbonnier, Vincent, Djavaheri-Mergny, Mojgan, Pietrocola, Federico, Sadoshima, Junichi, Chiara Maiuri, María, Martins, Isabelle, Kroemer, Guido
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/296251
Acceso en línea:http://hdl.handle.net/10261/296251
Access Level:acceso abierto
Palabra clave:Acyl-CoA binding protein
Autophagy
Non-alcoholic steatohepatitis
Myocardium infarction
Fibrosis
Descripción
Sumario: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.

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