Endothelial autophagy is not required for liver regeneration after partial hepatectomy in mice with fatty liver.

Autor: Hammoutene A; Université Paris Cité, PARCC, INSERM, Paris, France.; Université Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France., Tanguy M; Université Paris Cité, PARCC, INSERM, Paris, France.; Université Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France., Calmels M; Université Paris Cité, PARCC, INSERM, Paris, France., Pravisani R; Service de chirurgie hépatobiliaire et pancréatique, Hôpital Beaujon, AP-HP, Clichy, France., Albuquerque M; Université Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France.; Service d'Anatomie Pathologique, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France., Casteleyn C; Department of Morphology, Imaging, Orthopaedics, Physiotherapy and Nutrition, Ghent University, Ghent, Belgium., Slimani L; Laboratory of Orofacial Pathologies, Imaging and Biotherapies URP2496, Université Paris Cité, Montrouge, France.; Plateforme Imageries du Vivant, Faculté de Chirurgie Dentaire, Université Paris Cité, Montrouge, France., Sadoine J; Laboratory of Orofacial Pathologies, Imaging and Biotherapies URP2496, Université Paris Cité, Montrouge, France.; Plateforme Imageries du Vivant, Faculté de Chirurgie Dentaire, Université Paris Cité, Montrouge, France., Boulanger CM; Université Paris Cité, PARCC, INSERM, Paris, France., Paradis V; Université Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France.; Service d'Anatomie Pathologique, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France., Gilgenkrantz H; Université Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France., Rautou PE; Université Paris Cité, PARCC, INSERM, Paris, France.; Université Paris-Cité, Inserm, Centre de recherche sur l'inflammation, UMR 1149, Paris, France.; Service d'Hépatologie, AP-HP, Hôpital Beaujon, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France.
Jazyk: angličtina
Zdroj: Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2023 Oct; Vol. 43 (10), pp. 2309-2319. Date of Electronic Publication: 2023 Jul 04.
DOI: 10.1111/liv.15665
Abstrakt: Background & Aims: Patients with non-alcoholic fatty liver disease (NAFLD) have impaired liver regeneration. Liver endothelial cells play a key role in liver regeneration. In non-alcoholic steatohepatitis (NASH), liver endothelial cells display a defect in autophagy, contributing to NASH progression. We aimed to determine the role of endothelial autophagy in liver regeneration following liver resection in NAFLD.
Methods: First, we assessed autophagy in primary endothelial cells from wild type mice fed a high fat diet and subjected to partial hepatectomy. Then, we assessed liver regeneration after partial hepatectomy in mice deficient (Atg5 lox/lox ;VE-cadherin-Cre + ) or not (Atg5 lox/lox ) in endothelial autophagy and fed a high fat diet. The role of endothelial autophagy in liver regeneration was also assessed in ApoE -/- hypercholesterolemic mice and in mice with NASH induced by methionine- and choline-deficient diet.
Results: First, autophagy (LC3II/protein) was strongly increased in liver endothelial cells following hepatectomy. Then, we observed at 40 and 48 h and at 7 days after partial hepatectomy, that Atg5 lox/lox ;VE-cadherin-Cre + mice fed a high fat diet had similar liver weight, plasma AST, ALT and albumin concentration, and liver protein expression of proliferation (PCNA), cell-cycle (Cyclin D1, BrdU incorporation, phospho-Histone H3) and apoptosis markers (cleaved Caspase-3) as Atg5 lox/lox mice fed a high fat diet. Same results were obtained in ApoE -/- and methionine- and choline-deficient diet fed mice, 40 h after hepatectomy.
Conclusion: These results demonstrate that the defect in endothelial autophagy occurring in NASH does not account for the impaired liver regeneration occurring in this setting.
(© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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