scholarly journals The Role of Farnesoid X Receptor in Accelerated Liver Regeneration in Rats Subjected to ALPPS

2021 ◽  
Vol 28 (6) ◽  
pp. 5240-5254
Author(s):  
Noemi Daradics ◽  
Pim B. Olthof ◽  
Andras Budai ◽  
Michal Heger ◽  
Thomas M. van Gulik ◽  
...  
Keyword(s):  
Portal Vein ◽  
Liver Regeneration ◽  
Farnesoid X Receptor ◽  
Signaling Cascades ◽  
Portal Vein Ligation ◽  
Mrna Levels ◽  
Hemodynamic Changes ◽  
Regeneration Rate ◽  
Male Wistar Rats

Background: the role of bile acid (BA)-induced farnesoid X receptor (Fxr) signaling in liver regeneration following associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was investigated in a rat model. Methods: Male Wistar rats underwent portal vein ligation (PVL) (n = 30) or ALPPS (n = 30). Animals were sacrificed pre-operatively and at 24, 48, 72, or 168 h after intervention. Regeneration rate, Ki67 index, hemodynamic changes in the hepatic circulation, and BA levels were assessed. Transcriptome analysis of molecular regulators involved in the Fxr signaling pathway, BA transport, and BA production was performed. Results: ALLPS induced more extensive liver regeneration (p < 0.001) and elevation of systemic and portal BA levels (p < 0.05) than PVL. The mRNA levels of proteins participating in hepatic Fxr signaling were comparable between the intervention groups. More profound activation of the intestinal Fxr pathway was observed 24 h after ALPPS compared to PVL. Conclusion: Our study elaborates on a possible linkage between BA-induced Fxr signaling and accelerated liver regeneration induced by ALPPS in rats. ALPPS could trigger liver regeneration via intestinal Fxr signaling cascades instead of hepatic Fxr signaling, thereby deviating from the mechanism of BA-mediated regeneration following one-stage hepatectomy.

scholarly journals Reg3α and Reg3β Expressions Followed by JAK2/STAT3 Activation Play a Pivotal Role in the Acceleration of Liver Hypertrophy in a Rat ALPPS Model

2020 ◽  
Vol 21 (11) ◽  
pp. 4077
Author(s):  
Naohiko Otsuka ◽  
Masato Yoshioka ◽  
Yuki Abe ◽  
Yasuhiko Nakagawa ◽  
Hiroshi Uchinami ◽  
...  
Keyword(s):  
Portal Vein ◽  
Liver Regeneration ◽  
Inflammatory Cytokines ◽  
Inflammatory Cytokine ◽  
Janus Kinase ◽  
Portal Vein Ligation ◽  
Sprague Dawley ◽  
Regeneration Rate ◽  
Stat3 Pathway ◽  
Cytokine Levels

To explore the underlying mechanism of rapid liver hypertrophy by liver partition in associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), liver partition at different sites was investigated. Increased inflammatory cytokines owing to the liver partition have been reportedly responsible. If this were true, rapid liver hypertrophy should be achieved regardless of where the liver was split. A male Sprague-Dawley rat model was created, in which a liver split was placed inside the portal vein ligated lobe (PiLL), in addition to the ALPPS and portal vein ligation (PVL) models. Liver regeneration rate, inflammatory cytokine levels, activation status of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway and expressions of regenerating islet-derived (Reg)3α and Reg3β were investigated. The liver regeneration rate was significantly higher in the ALPPS group than in the PiLL group, whereas inflammatory cytokine levels were nearly equal. Additional volume increase in ALPPS group over PVL and PiLL groups was JAK2/STAT3-dependent. Reg3α and Reg3β expressions were observed only in the ALPPS group. An increase in inflammatory cytokines was not enough to describe the mechanism of rapid liver hypertrophy in ALPPS. Expressions of Reg3α and Reg3β could play an important role in conjunction with an activation of the JAK2/STAT3 pathway.

The Contemporary Role of Resection and Ablation in Colorectal Cancer Liver Metastases

2020 ◽  
Vol 04 (03) ◽  
pp. 291-302
Author(s):  
Mariam F. Eskander ◽  
Christopher T. Aquina ◽  
Aslam Ejaz ◽  
Timothy M. Pawlik
Keyword(s):  
Colorectal Cancer ◽  
Portal Vein ◽  
Surgical Oncology ◽  
Portal Vein Ligation ◽  
Safe Alternative ◽  
Colorectal Cancer Liver Metastases ◽  
Liver Remnant ◽  
New Era ◽  
Ablation Therapy

AbstractAdvances in the field of surgical oncology have turned metastatic colorectal cancer of the liver from a lethal disease to a chronic disease and have ushered in a new era of multimodal therapy for this challenging illness. A better understanding of tumor behavior and more effective systemic therapy have led to the increased use of neoadjuvant therapy. Surgical resection remains the gold standard for treatment but without the size, distribution, and margin restrictions of the past. Lesions are considered resectable if they can safely be removed with tumor-free margins and a sufficient liver remnant. Minimally invasive liver resections are a safe alternative to open surgery and may offer some advantages. Techniques such as portal vein embolization, association of liver partition with portal vein ligation for staged hepatectomy, and radioembolization can be used to grow the liver remnant and allow for resection. If resection is not possible, nonresectional ablation therapy, including radiofrequency and microwave ablation, can be performed alone or in conjunction with resection. This article presents the most up-to-date literature on resection and ablation, with a discussion of current controversies and future directions.

Role of nuclear receptors and hepatocyte-enriched transcription factors for Ntcp repression in biliary obstruction in mouse liver

2005 ◽  
Vol 289 (5) ◽  
pp. G798-G805 ◽  
Author(s):  
Gernot Zollner ◽  
Martin Wagner ◽  
Peter Fickert ◽  
Andreas Geier ◽  
Andrea Fuchsbichler ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Bile Acid ◽  
Dna Binding ◽  
Nuclear Receptors ◽  
Farnesoid X Receptor ◽  
Acid Uptake ◽  
Mrna Levels ◽  
Uptake System ◽  
Duct Ligation

Expression of the main hepatic bile acid uptake system, the Na+-taurocholate cotransporter (Ntcp), is downregulated during cholestasis. Bile acid-induced, farnesoid X receptor (FXR)-mediated induction of the nuclear repressor short heterodimer partner (SHP) has been proposed as a key mechanism reducing Ntcp expression. However, the role of FXR and SHP or other nuclear receptors and hepatocyte-enriched transcription factors in mediating Ntcp repression in obstructive cholestasis is unclear. FXR knockout (FXR−/−) and wild-type (FXR+/+) mice were subjected to common bile duct ligation (CBDL). Cholic acid (CA)-fed and LPS-treated FXR−/− and FXR+/+ mice were studied for comparison. mRNA levels of Ntcp and SHP and nuclear protein levels of hepatocyte nuclear factor (HNF)-1α, HNF-3β, HNF-4α, retinoid X receptor (RXR)-α, and retinoic acid receptor (RAR)-α and their DNA binding were assessed. Hepatic cytokine mRNA levels were also measured. CBDL and CA led to Ntcp repression in FXR+/+, but not FXR−/−, mice, whereas LPS reduced Ntcp expression in both genotypes. CBDL and LPS but not CA induced cytokine expression and reduced levels of HNF-1α, HNF-3β, HNF-4α, RXRα, and RARα to similar extents in FXR+/+ and FXR−/−. DNA binding of these transactivators was unaffected by CA in FXR+/+ mice but was markedly reduced in FXR−/− mice. In conclusion, Ntcp repression by CBDL and CA is mediated by accumulating bile acids via FXR and does not depend on cytokines, whereas Ntcp repression by LPS is independent of FXR. Reduced levels of HNF-1α, RXRα, and RARα in CBDL FXR−/− mice and reduced DNA binding in CA-fed FXR−/− mice, despite unchanged Ntcp levels, indicate that these factors may have a minor role in regulation of mouse Ntcp during cholestasis.

scholarly journals Effect of Portal Vein Ligation Plus Venous Congestion on Liver Regeneration in Rats

2019 ◽  
Vol 18 (1) ◽  
pp. 89-100
Author(s):  
Daisuke Kawaguchi ◽  
Yukihiko Hiroshima ◽  
Takafumi Kumamoto ◽  
Ryutaro Mori ◽  
Ryusei Matsuyama ◽  
...  
Keyword(s):  
Portal Vein ◽  
Liver Regeneration ◽  
Venous Congestion ◽  
Portal Vein Ligation

scholarly journals Role of associating liver partition and portal vein ligation in staged hepatectomy (ALPPS)—strategy for colorectal liver metastases

2018 ◽  
Vol 3 ◽  
pp. 66-66 ◽  
Author(s):  
Arezou Abbasi ◽  
Amir A. Rahnemai-Azar ◽  
Katiuscha Merath ◽  
Sharon M. Weber ◽  
Daniel E. Abbott ◽  
...  
Keyword(s):  
Portal Vein ◽  
Liver Metastases ◽  
Colorectal Liver Metastases ◽  
Portal Vein Ligation ◽  
Staged Hepatectomy

Ischemia/Reperfusion in Clamped Lobes Facilitates Liver Regeneration of Non-clamped Lobes After Selective Portal Vein Ligation

2012 ◽  
Vol 57 (12) ◽  
pp. 3178-3183 ◽  
Author(s):  
Jian-hua Yu ◽  
Wei-guang Zhang ◽  
Gui-xing Jiang ◽  
Jia-yun Zhao ◽  
Hui Li ◽  
...  
Keyword(s):  
Portal Vein ◽  
Liver Regeneration ◽  
Ischemia Reperfusion ◽  
Portal Vein Ligation

scholarly journals Transection of the hepatic parenchyma associated or not with the contralateral portal vein branch ligature and its effect in liver regeneration

2017 ◽  
Vol 15 (2) ◽  
pp. 178-185
Author(s):  
Henrique de Aguiar Wiederkehr ◽  
Julio Cesar Wiederkehr ◽  
Luiz Martins Collaço ◽  
Eros Luiz de Sousa ◽  
Paolo Salvalaggio ◽  
...  
Keyword(s):  
Liver Resection ◽  
Portal Vein ◽  
Liver Regeneration ◽  
Inflammatory Cells ◽  
Hepatic Regeneration ◽  
Portal Vein Ligation ◽  
Portal Vein Branch ◽  
Regeneration Status ◽  
Left Portal Vein ◽  
Two Stages

ABSTRACT Objective To analyze the influence of portal vein ligation in hepatic regeneration by immunohistochemical criteria. Methods Ten pigs divided into two groups of five animals underwent hepatectomy in two stages, and the groups were differentiated by ligation or not of the left portal vein tributary, which is responsible for vascularization of the left lateral and medial lobes of the pig liver. Five days after the procedure, the animals underwent liver biopsies for further analysis of histological and immunohistochemical with marker Ki67. Results The group submitted to hepatectomy with vascular ligation showed an increase of approximately 4% of hepatocytes in regeneration status, as well as a greater presence of Kupffer and inflammatory cells as compared to control. Conclusion As a result of positive cell replication observed through the Ki67 marker, we can suspect that the ligation of a tributary of the portal vein associated with liver resection promoted a greater stimulus of liver regeneration when compared to liver resection alone.

scholarly journals Folinic Acid Potentiates the Liver Regeneration Process after Selective Portal Vein Ligation in Rats

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 371
Author(s):  
Jorge Gutiérrez Sáenz de Santa María ◽  
Borja Herrero de la Parte ◽  
Gaizka Gutiérrez-Sánchez ◽  
Inmaculada Ruiz Montesinos ◽  
Sira Iturrizaga Correcher ◽  
...  
Keyword(s):  
Liver Function ◽  
Portal Vein ◽  
Liver Regeneration ◽  
Folinic Acid ◽  
Hepatic Metastases ◽  
Future Liver Remnant ◽  
Control Group ◽  
Portal Vein Ligation ◽  
Nuclear Area ◽  
Liver Remnant

Liver resection remains the gold standard for hepatic metastases. The future liver remnant (FLR) and its functional status are two key points to consider before performing major liver resections, since patients with less than 25% FLR or a Child–Pugh B or C grade are not eligible for this procedure. Folinic acid (FA) is an essential agent in cell replication processes. Herein, we analyze the effect of FA as an enhancer of liver regeneration after selective portal vein ligation (PVL). Sixty-four male WAG/RijHsd rats were randomly distributed into eight groups: a control group and seven subjected to 50% PVL, by ligation of left portal branch. The treated animals received FA (2.5 m/kg), while the rest were given saline. After 36 h, 3 days or 7 days, liver tissue and blood samples were obtained. FA slightly but significantly increased FLR percentage (FLR%) on the 7th day (91.88 ± 0.61%) compared to control or saline-treated groups (86.72 ± 2.5 vs. 87 ± 3.33%; p < 0.01). The hepatocyte nuclear area was also increased both at 36 h and 7days with FA (61.55 ± 16.09 µm2, and 49.91 ± 15.38 µm2; p < 0.001). Finally, FA also improved liver function. In conclusion, FA has boosted liver regeneration assessed by FLR%, nuclear area size and restoration of liver function after PVL.

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