IL-22 promotes liver regeneration after portal vein ligation
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IL-22 promotes liver regeneration after portal vein ligation. / Zhang, Tao; Seeger, Philipp; Simsek, Yashin J; Sabihi, Morsal; Lücke, Jöran; Zazara-Giannou, Dimitra; Shiri, Mustafa; Kempski, Jan Michael; Blankenburg, Tom; Zhao, Lilan; Belios, Ioannis; Machicote, Andres Pablo; Mercanoglu, Baris; Fard-Aghaie, Mohammad; Notz, Sara Johanna; Lykoudis, Panagis M; Kemper, Marius; Ghadban, Tarik; Mann, Oliver; Hackert, Thilo; Izbicki, Jakob; Renne, Thomas; Huber, Samuel; Giannou, Anastasios; Li, Jun.
in: HELIYON, Jahrgang 10, Nr. 6, 30.03.2024, S. e27578.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - IL-22 promotes liver regeneration after portal vein ligation
AU - Zhang, Tao
AU - Seeger, Philipp
AU - Simsek, Yashin J
AU - Sabihi, Morsal
AU - Lücke, Jöran
AU - Zazara-Giannou, Dimitra
AU - Shiri, Mustafa
AU - Kempski, Jan Michael
AU - Blankenburg, Tom
AU - Zhao, Lilan
AU - Belios, Ioannis
AU - Machicote, Andres Pablo
AU - Mercanoglu, Baris
AU - Fard-Aghaie, Mohammad
AU - Notz, Sara Johanna
AU - Lykoudis, Panagis M
AU - Kemper, Marius
AU - Ghadban, Tarik
AU - Mann, Oliver
AU - Hackert, Thilo
AU - Izbicki, Jakob
AU - Renne, Thomas
AU - Huber, Samuel
AU - Giannou, Anastasios
AU - Li, Jun
PY - 2024/3/30
Y1 - 2024/3/30
N2 - BackgroundInsufficient 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.MethodsLiver 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.ResultsThe 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.ConclusionIL-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.
AB - BackgroundInsufficient 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.MethodsLiver 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.ResultsThe 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.ConclusionIL-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.
U2 - 10.1016/j.heliyon.2024.e27578
DO - 10.1016/j.heliyon.2024.e27578
M3 - SCORING: Journal article
C2 - 38533053
VL - 10
SP - e27578
JO - HELIYON
JF - HELIYON
SN - 2405-8440
IS - 6
ER -