title: Autophagy: a multifaceted partner in liver fibrosis.
abstract: Liver fibrosis is a common wound healing response to chronic liver injury of all causes, and its end-stage cirrhosis is responsible for high morbidity and mortality worldwide. Fibrosis results from prolonged parenchymal cell apoptosis and necrosis associated with an inflammatory reaction that leads to recruitment of immune cells, activation and accumulation of fibrogenic cells, and extracellular matrix accumulation. The fibrogenic process is driven by hepatic myofibroblasts, that mainly derive from hepatic stellate cells undergoing a transdifferentiation from a quiescent, lipid-rich into a fibrogenic myofibroblastic phenotype, in response to paracrine/autocrine signals produced by neighbouring inflammatory and parenchymal cells. Autophagy is an important regulator of liver homeostasis under physiological and pathological conditions. This review focuses on recent findings showing that autophagy is a novel, but complex, regulatory pathway in liver fibrosis, with profibrogenic effects relying on its direct contribution to the process of hepatic stellate cell activation, but with antifibrogenic properties via indirect hepatoprotective and anti-inflammatory properties. Therefore, cell-specific delivery of drugs that exploit autophagic pathways is a prerequisite to further consider autophagy as a potential target for antifibrotic therapy.
authors.affiliation: INSERM U955, 94000 Créteil, France ; Université Paris-Est, Faculté de Médecine, UMR-S955, 94000 Créteil, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Mallat
authors.affiliation: INSERM U1149, Center for Research on Inflammation, 75018 Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, 75018 Paris, France ; Laboratoire d'Excellence Inflamex, 75018 Paris, France.
authors.forename: Jasper
authors.identifier: 0000-0002-1963-835X
authors.initials: J
authors.lastname: Lodder
authors.affiliation: INSERM U955, 94000 Créteil, France ; Université Paris-Est, Faculté de Médecine, UMR-S955, 94000 Créteil, France.
authors.forename: Fatima
authors.initials: F
authors.lastname: Teixeira-Clerc
authors.affiliation: INSERM U1149, Center for Research on Inflammation, 75018 Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, 75018 Paris, France ; Laboratoire d'Excellence Inflamex, 75018 Paris, France ; Département Hospitalo-Universitaire (DHU) UNITY, Service d'Hépatologie, Hôpital Beaujon, AP-HP, 92000 Clichy, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Moreau
authors.affiliation: INSERM U1151-CNRS UMR8223, INEM, 75014 Paris, France ; Université Paris-Descartes, Sorbonne Paris Cité, Site Necker Enfants-Malades, 75015 Paris, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Codogno
authors.affiliation: INSERM U1149, Center for Research on Inflammation, 75018 Paris, France ; Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, 75018 Paris, France ; Laboratoire d'Excellence Inflamex, 75018 Paris, France ; Département Hospitalo-Universitaire (DHU) UNITY, Service d'Hépatologie, Hôpital Beaujon, AP-HP, 92000 Clichy, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lotersztajn
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D054338:Cell Transdifferentiation / Q000235:genetics; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D055166:Hepatic Stellate Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents