IL-22 promotes liver regeneration after portal vein ligation
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-2...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-03-01
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| Series: | Heliyon |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024036090 |
| _version_ | 1827294061442105344 |
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| author | Tao Zhang Philipp Seeger Yashin Simsek Morsal Sabihi Jöran Lücke Dimitra E. Zazara Ahmad Mustafa Shiri Jan Kempski Tom Blankenburg Lilan Zhao Ioannis Belios Andres Machicote Baris Mercanoglu Mohammad Fard-Aghaie Sara Notz Panagis M. Lykoudis Marius Kemper Tarik Ghadban Oliver Mann Thilo Hackert Jakob R. Izbicki Thomas Renné Samuel Huber Anastasios D. Giannou Jun Li |
| author_facet | Tao Zhang Philipp Seeger Yashin Simsek Morsal Sabihi Jöran Lücke Dimitra E. Zazara Ahmad Mustafa Shiri Jan Kempski Tom Blankenburg Lilan Zhao Ioannis Belios Andres Machicote Baris Mercanoglu Mohammad Fard-Aghaie Sara Notz Panagis M. Lykoudis Marius Kemper Tarik Ghadban Oliver Mann Thilo Hackert Jakob R. Izbicki Thomas Renné Samuel Huber Anastasios D. Giannou Jun Li |
| author_sort | Tao Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T13:49:51Z |
| format | Article |
| id | doaj.art-e149ef093eb041cda71966c12d3904a4 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T13:49:51Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-e149ef093eb041cda71966c12d3904a42024-04-04T05:05:11ZengElsevierHeliyon2405-84402024-03-01106e27578IL-22 promotes liver regeneration after portal vein ligationTao Zhang0Philipp Seeger1Yashin Simsek2Morsal Sabihi3Jöran Lücke4Dimitra E. Zazara5Ahmad Mustafa Shiri6Jan Kempski7Tom Blankenburg8Lilan Zhao9Ioannis Belios10Andres Machicote11Baris Mercanoglu12Mohammad Fard-Aghaie13Sara Notz14Panagis M. Lykoudis15Marius Kemper16Tarik Ghadban17Oliver Mann18Thilo Hackert19Jakob R. Izbicki20Thomas Renné21Samuel Huber22Anastasios D. Giannou23Jun Li24Section 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, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanySection 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, GermanySection 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, GermanyDivision 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, GermanySection of Molecular Immunology and Gastroenterology, I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, GermanySection 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, GermanySection 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, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, GermanyDivision for Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg 20246, GermanySection 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, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany3rd Department of Surgery, National & Kapodistrian University of Athens, Greece; Division of Surgery & Interventional Science, University College London (UCL), UKDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, GermanyDepartment of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, GermanyInstitute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanySection 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, GermanySection 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; Corresponding author. University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20251, Germany.Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany; Corresponding author. University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20251, Germany.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.http://www.sciencedirect.com/science/article/pii/S2405844024036090 |
| spellingShingle | Tao Zhang Philipp Seeger Yashin Simsek Morsal Sabihi Jöran Lücke Dimitra E. Zazara Ahmad Mustafa Shiri Jan Kempski Tom Blankenburg Lilan Zhao Ioannis Belios Andres Machicote Baris Mercanoglu Mohammad Fard-Aghaie Sara Notz Panagis M. Lykoudis Marius Kemper Tarik Ghadban Oliver Mann Thilo Hackert Jakob R. Izbicki Thomas Renné Samuel Huber Anastasios D. Giannou Jun Li IL-22 promotes liver regeneration after portal vein ligation Heliyon |
| title | IL-22 promotes liver regeneration after portal vein ligation |
| title_full | IL-22 promotes liver regeneration after portal vein ligation |
| title_fullStr | IL-22 promotes liver regeneration after portal vein ligation |
| title_full_unstemmed | IL-22 promotes liver regeneration after portal vein ligation |
| title_short | IL-22 promotes liver regeneration after portal vein ligation |
| title_sort | il 22 promotes liver regeneration after portal vein ligation |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024036090 |
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