IL-22 promotes liver regeneration after portal vein ligation.

Autor:	Zhang T; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Seeger P; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany., Simsek Y; Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Sabihi M; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Lücke J; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany., Zazara DE; Division for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.; University Children's Hospital, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany., Shiri AM; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany., Kempski J; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.; Mildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Blankenburg T; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Zhao L; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany., Belios I; Division for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany., Machicote A; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Mercanoglu B; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany., Fard-Aghaie M; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany., Notz S; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany., Lykoudis PM; 3rd Department of Surgery, National & Kapodistrian University of Athens, Greece.; Division of Surgery & Interventional Science, University College London (UCL), UK., Kemper M; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany., Ghadban T; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany., Mann O; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany., Hackert T; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany., Izbicki JR; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany., Renné T; Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Huber S; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany., Giannou AD; Section of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.; Hamburg Center for Translational Immunology (HCTI), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany., Li J; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.
Jazyk:	angličtina
Zdroj:	Heliyon [Heliyon] 2024 Mar 08; Vol. 10 (6), pp. e27578. Date of Electronic Publication: 2024 Mar 08 (Print Publication: 2024).
DOI:	10.1016/j.heliyon.2024.e27578
Abstrakt:	Background: Insufficient remnant liver volume (RLV) after the resection of hepatic malignancy could lead to liver failure and mortality. Portal vein ligation (PVL) prior to hepatectomy is subsequently introduced to increase the remnant liver volume and improve the outcome of hepatic malignancy. IL-22 has previously been reported to promote liver regeneration, while facilitating tumor development in the liver via Steap4 upregulation. Here we performed PVL in mouse models to study the role of IL-22 in liver regeneration post-PVL. Methods: Liver weight and volume was measured via magnetic resonance imaging (MRI). Immunohistochemistry for Ki67 and hepatocyte growth factor (HGF) was performed. IL-22 was analyzed by flow cytometry and quantitative polymerase chain reaction (qPCR) was used for acquisition of Il-33, Steap4, Fga, Fgb and Cebpd . To analyze signaling pathways, mice with deletion of STAT3 and a neutralizing antibody for IL-22 were used. Results: The remnant liver weight and volume increased over time after PVL. Additionally, we found that liver regenerative molecules, including Ki67 and HGF, were significantly increased in remnant liver at day 3 post-PVL, as well as IL-22. Administration of IL-22 neutralizing antibody could reduce Ki67 expression after PVL. The upregulation of IL-22 after PVL was mainly derived from innate cells. IL-22 blockade resulted in lower levels of IL-33 and Steap4 in the remnant liver, which was also the case in mice with deletion of STAT3, the main downstream signaling molecule of IL-22, in hepatocytes. Conclusion: IL-22 promotes liver regeneration after PVL. Thus, a combination of IL-22 supplementation and Steap4 blockade could potentially be applied as a novel therapeutic approach to boost liver regeneration without facilitating tumor progression after PVL. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2024 The Authors.)
Databáze:	MEDLINE
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