The role of farnesoid X receptor in accelerated liver regeneration in rats subjected to ALPPS

Noemi Daradics*, Pim B. Olthof, Andras Budai, Michal Heger, Thomas M. van Gulik, Andras Fulop, Attila Szijarto

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Pages (from-to)5240-5254
Number of pages15
JournalCurrent Oncology
Volume28
Issue number6
DOIs
Publication statusPublished - 9 Dec 2021

Bibliographical note

Funding Information:
This work was supported by the European Society of Surgical Research. N.D. is supported by the ?New National Excellence Program of the Ministry of Human Capacities of Hungary? (?NKP-20-3-I-SE-9; N.D.) and Semmelweis University 250+ PhD Excellence Grant (EFOP-3.6.3-VEKOP-16-2017 00009). AF is supported by Bolyai J?nos Research Grant of the Hungarian Academy of Sciences. M.H. is supported by grants from the Dutch Cancer Foundation (KWF project # 10666), a Zhejiang Provincial Foreign Expert Program Grant, and Zhejiang Provincial Key Natural Science Foundation of China (#Z20H160031), and a grant for the establishment of the Jiaxing Key Laboratory for Photonanomedicine and Experimental Therapeutics.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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