Data report on gene expression after hepatic portal vein ligation (PVL) in rats.
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SUBMITTER: Meyer D
PROVIDER: S-EPMC11371715 | biostudies-literature | 2024
REPOSITORIES: biostudies-literature
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Data report on gene expression after hepatic portal vein ligation (PVL) in rats.
Meyer Daria D Kosacka Joanna J von Bergen Martin M Christ Bruno B Marz Manja M
Frontiers in genetics 20240821
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Project description:The effects of acute portal hypertension (PHT), which is reported as poor prognostic factors in patients with hepatocellular carcinoma, are not well known on the liver immune system, including natural killer (NK) cells. The aim of this study, therefore, was to investigate how acute PHT influences the functions and characteristics of liver-resident NK (lr-NK) cells using an acute PHT mouse model. Acute PHT decreased the number of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL+ ) lr-NK cells by about 20% and attenuated cytotoxic activity against the Hepa1-6 cell line by about 40%. Among various cytokine, only interleukin-33 (IL-33), which inhibits NK activity, significantly increased after portal vein ligation (PVL). Because lr-NK cells highly expressed ST2/IL-33R, IL-33 co-culture significantly suppressed TRAIL expression on lr-NK cells by about 50%, and IL-33 administration markedly decreased TRAIL expression and cytotoxic activity of lr-NK cells. Furthermore, the TRAIL+ NK cells population was maintained by anti-IL33 antibody or following portosystemic shunt procedure even after PVL. Finally, we demonstrated that IL-33 decreased TRAIL expression in lr-NK cells via AKT-forkhead box O (FoxO) and mitogen-activated protein kinase (MAPK) signaling. Conclusion: This work demonstrates that PHT suppresses the TRAIL+ lr-NK cell population and antitumor activities in the liver. Additionally, Akt-FoxO and MAPK signaling pathways attenuate the TRAIL expression in lt-NK cells via IL-33 receptor in mice.
| S-EPMC9426399 | biostudies-literature
Project description:Background and Aims The aim was to establish a liver venous deprivation (LVD) model in rats, compare hepatic hypertrophy between LVD and associated liver partition and portal vein ligation for staged hepatectomy (ALPPS), and explore the underlying mechanisms. Methods The LVD or extended-LVD (e-LVD) group received portal vein ligation (PVL) combined with hepatic vein ligation (HVL). The ALPPS or e-ALPPS group received PVL plus parenchyma ligation. Liver regeneration was assessed by measuring the liver weight and performing pathological analysis. Liver functions and the sphingosine kinase 1 (SPHK1)/sphingosine-1-phosphate (S1P)/sphingosine-1-phosphate receptor 1 (S1PR1) pathway were also investigated. Results All future liver remnants (FLRs) in the ALPPS, e-ALPPS, LVD, and e-LVD groups exhibited significant hypertrophy compared with the control group. The LVD and e-LVD procedures induced similar liver hypertrophy than that in the corresponding ALPPS groups. Furthermore, the LVD and e-LVD methods led to obvious cytolysis in the venous-deprived lobes as well as a noticeable increase in serum transaminase levels, while no necrosis was observed in the ALPPS and e-ALPPS groups. SPHK1/S1P/S1PR1 pathway were distinctly activated after operation, especially in congestive/ischemic livers. Conclusions We describe the first rat model of LVD and e-LVD with simultaneously associated HVL and PVL. Compared with the ALPPS technique, the LVD or e-LVD procedure had a comparable overall effect on the hypertrophy response and a stronger effect on liver function. The SPHK1/S1P/S1PR1 pathway was involved in the LVD- or ALPPS-induced liver remodeling. Graphical abstract
| S-EPMC9817047 | biostudies-literature
Project description:Portal vein ligation (PVL) induces atrophy/hypertrophy complex (AHC). We hypothesised that simultaneous bile duct and portal vein ligation (BPL) might induce proper bile acid (BA) retention to enhance AHC by activating BA-mediated FXR signalling in the intact liver and promoting apoptosis in the ligated liver. We established rat models of 90% BPL and 90% PVL and found that BPL was well-tolerated and significantly accelerated AHC. The enhanced BA retention in the intact liver promoted hepatocyte proliferation by promoting the activation of FXR signalling, while that in the ligated liver intensified caspase3-mediated apoptosis. Decreasing the BA pools in the rats that underwent BPL could compromise these effects, whereas increasing the bile acid pools of rats that underwent PVL could induce similar effects. Second-stage resection of posterior-caudate-lobe-spearing hepatectomy was performed 5 days after BPL (B-Hx), PVL (V-Hx) or sham (S-SHx), as well as whole-caudate-lobe-spearing hepatectomy 5 days after sham (S-Hx). The B-Hx group had the most favourable survival rate (93.3%, the S-SHx group 0%, the S-Hx group 26.7%, the V-Hx group 56.7%, P < 0.01) and the most sustained regeneration. We conclude that BPL is a safe and effective method, and the acceleration of AHC was bile acid-dependent.
| S-EPMC4326731 | biostudies-literature
Project description:We compared transcriptomic profiles of hepatic macrophages between sham operated rats, rats 3 days and 10 days after partial portal vein ligation (PPVL) surgery (n=3). The number of genes with a significant change was most numerous in Sham vs 3 days, followed by Sham vs 10 days and 3 days vs 10 days.
2019-01-01 | GSE117467 | GEO
Project description:BackgroundAssociating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was introduced in 2007. The current study explored the mechanisms of rapid liver hypertrophy after ALPPS in cirrhotic rats.MethodsA cirrhotic rat model was constructed and portal vein ligation (PVL) or ALPPS treatments were administered. The liver hyperplasia rate of the rats was calculated, and hepatic function was evaluated using biochemical factors and the indocyanine green excretion test. Subsequently, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and hematoxylin and eosin (HE) staining were performed to determine the degree of liver regeneration. Differentially expressed genes during the rapid liver hypertrophy were detected by bioinformatics analysis, followed verification using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry.ResultsThe body weight of rats that underwent PVL and ALPPS changed during the first 1-4 days postoperatively, and the alterations were more pronounced in rats receiving ALPPS. The recovery of body weight in cirrhotic rats was slower than that in normal rats. The levels of biochemical factors and the indocyanine green retention rate increased 1 day after PVL and ALPPS, and then decreased gradually. PVL and ALPPS elevated the levels of cytokines, inflammatory factors, and proliferating cell nuclear antigen (PCNA) in rats at 1 day postoperatively. HE observation of rat liver condition showed that rats recovered faster within the first 4 days postoperatively. ALPPS surgery resulted in a significant downregulation of matrix metalloproteinase (MMP)2/9 expression in cirrhotic rats at postoperative day 4.ConclusionsLiver function was partially recovered in cirrhotic rats after ALPPS, and the underlying mechanisms may involve PCNA and MMP2/9.
| S-EPMC9096403 | biostudies-literature
Project description: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.
| S-EPMC10963228 | biostudies-literature
Project description:BackgroundVarious techniques, including portal vein embolization (PVE), contralateral portal vein ligation (PVL) and associating liver partition and portal vein ligation (ALPPS), are being used to augment the future liver remnant (FLR) volume in preparation for a major hepatectomy. The present study aims to survey and document the availability, variation, utilization and attitudes toward these techniques across centres in North and South America.MethodsA descriptive, 20-question survey was developed and internally validated with expert review. The survey was distributed to 115 centres in North and South America.ResultsOf the 115 centres, 54 institutions (47%) returned the surveys. Regarding the question of which modality was most likely to produce adequate hypertrophy, the respondents were equally distributed (ALPPS, 37%; PVE, 35%; equal, 22%). The procedure that respondents judged the safest to achieve liver hypertrophy was PVE (82%). Institutions with capability to extended PVE to segment IV rated the likelihood of PVE technical success (6.2 versus 8.5, P = 0.012) and likelihood of subsequent hypertrophy (5.6 versus 7.8, P = 0.011) higher than institutions without this capability. Although the use of modern embolic materials was associated with a likelihood of successful PVE (P = 0.032), only 49% of respondents who performed PVE used embolic microspheres.ConclusionsThere exists significant variability in utilization of and attitudes towards the available techniques for FLR volume augmentation. Penetration of best practice techniques for PVE is lacking, and may be contributing towards disappointment with PVE efficacy, potentially motivating the utilization of the riskier ALPPS procedure.
| S-EPMC4571762 | biostudies-literature
Project description:Selective portal vein ligation (PVL) allows the two-stage surgical resection of primarily unresectable liver tumours by generating the atrophy and hypertrophy of portally ligated (LL) and non-ligated lobes (NLL), respectively. To evaluate critically important underlying functional alterations, present study characterised in vitro and vivo liver function in male Wistar rats (n = 106; 210-250 g) before, and 24/48/72/168/336 h after PVL. Lobe weights and volumes by magnetic resonance imaging confirmed the atrophy-hypertrophy complex. Proper expression and localization of key liver transporters (Ntcp, Bsep) and tight junction protein ZO-1 in isolated hepatocytes demonstrated constantly present viable and well-polarised cells in both lobes. In vitro taurocholate and bilirubin transport, as well as in vivo immunohistochemical Ntcp and Mrp2 expressions were bilaterally temporarily diminished, whereas LL and NLL structural acinar changes were divergent. In vivo bile and bilirubin-glucuronide excretion mirrored macroscopic changes, whereas serum bilirubin levels remained unaffected. In vivo functional imaging (indocyanine-green clearance test; 99mTc-mebrofenin hepatobiliary scintigraphy; confocal laser endomicroscopy) indicated transitionally reduced global liver uptake and -excretion. While LL functional involution was permanent, NLL uptake and excretory functions recovered excessively. Following PVL, functioning cells remain even in LL. Despite extensive bilateral morpho-functional changes, NLL functional increment restores temporary declined transport functions, emphasising liver functional assessment.
| S-EPMC5741735 | biostudies-literature
Project description:BACKGROUND: Patients noted to have an inadequate future liver remnant on pre operative volumetric assessment are considered to be candidates for portal vein embolization (PVE). A subset of patients undergo laparoscopic intervention prior to PVE for staging purposes or to address the primary in Stage IV colon cancer. These patients usually undergo PVE as a subsequent additional procedure by the transhepatic route. The aim of this study was to assess the feasibility of portal vein ligation by the laparoscopic approach in suitable patients. MATERIALS AND METHODS: A retrospective review of a prospectively maintained database was performed to identify patients that underwent laparoscopic portal vein ligation (LPVL). The demographic, clinical, radiographic, operative and volumetric details were collected to determine the feasibility of portal vein ligation. RESULTS: A total of nine patients underwent LPVL as part of a two stage procedure in preparation for subsequent major hepatectomy. With a median age of 67 yrs, the diagnoses included: colorectal metastasis (five patients), cholangiocarcinoma (three patients) and hepatocellular carcinoma (one patient). The ligation involved the right portal vein in all and was performed with silk ligature (seven patients) and clips (two patients). Volumetric data was available in six patients which showed a mean increase from 209.1 cc+/-97.76 to 495.83 cc+/-310.91 (increase by 181.5%) In two patients, inadequate hypertrophy mandated later embolization by percutaneous technique. Five patients underwent subsequent major hepatic resection as planned. The remaining four patients were noted to have progression of disease that precluded the planned procedure. There were no complications associated with LPVL. CONCLUSIONS: LPVL is feasible and can be safely performed. In a select group of patients, it may be considered as an alternative to subsequent embolization and thereby potentially absolve the need for an additional procedure with its attendant complications.
| S-EPMC2518294 | biostudies-other
Project description:BackgroundMany patients with bi-lobar liver tumours are not eligible for liver resection due to an insufficient future liver remnant (FLR). To reduce the risk of posthepatectomy liver failure and the primary cause of death, regenerative procedures intent to increase the FLR before surgery. The aim of this systematic review is to provide an overview of the available literature and outcomes on the effectiveness of simultaneous portal and hepatic vein embolization (PVE/HVE) versus portal vein embolization (PVE) alone.MethodsA systematic literature search was conducted in PubMed, Web of Science, and Embase up to September 2022. The primary outcome was resectability and the secondary outcome was the FLR volume increase.ResultsEight studies comparing PVE/HVE with PVE and six retrospective PVE/HVE case series were included. Pooled resectability within the comparative studies was 75 per cent in the PVE group (n = 252) versus 87 per cent in the PVE/HVE group (n = 166, OR 1.92 (95% c.i., 1.13-3.25)) favouring PVE/HVE (P = 0.015). After PVE, FLR hypertrophy between 12 per cent and 48 per cent (after a median of 21-30 days) was observed, whereas growth between 36 per cent and 67 per cent was reported after PVE/HVE (after a median of 17-31 days). In the comparative studies, 90-day primary cause of death was similar between groups (2.5 per cent after PVE versus 2.2 per cent after PVE/HVE), but a higher 90-day primary cause of death was reported in single-arm PVE/HVE cohort studies (6.9 per cent, 12 of 175 patients).ConclusionBased on moderate/weak evidence, PVE/HVE seems to increase resectability of bi-lobar liver tumours with a comparable safety profile. Additionally, PVE/HVE resulted in faster and more pronounced hypertrophy compared with PVE alone.
| S-EPMC9702575 | biostudies-literature