The role of Toll-like receptors in liver regeneration
after partial hepatectomy

Spyridon Dritsas; Maximos Frountzas; Dimitrios Schizas; Francesk Mulita; Michalis Katsimpoulas; Paraskevas Gkolfakis; Irene Lidoriki; Ioannis Karavokyros; Elias Liolis; Evangelos Missiakos; Theodore Liakakos; Alkistis Kapelouzou

doi:10.5114/pg.2025.154724

eISSN: 1897-4317
ISSN: 1895-5770

Gastroenterology Review/Przegląd Gastroenterologiczny

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3/2025
vol. 20

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abstract:

Original paper

The role of Toll-like receptors in liver regeneration after partial hepatectomy

Spyridon Dritsas

¹

,

Maximos Frountzas

²

,

Dimitrios Schizas

³

,

Francesk Mulita

⁴

,

Michalis Katsimpoulas

⁵

,

Paraskevas Gkolfakis

⁶

,

Irene Lidoriki

³

,

Ioannis Karavokyros

³

,

Elias Liolis

⁷

,

Evangelos Missiakos

⁸

,

Theodore Liakakos

³

,

Alkistis Kapelouzou

⁹

Surgical Oncology, Evangelismos General Hospital, Athens, Greece
First Propaedeutic Department of Surgery, “Hippocration” General Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece
First Department of Surgery, Laikon Hospital, Medical School, National and Kapodistrian University of Athens, Greece
Department of Surgery, University General Hospital of Patras, Greece
Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Greece
Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, CUB Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium
Department of Oncology, University General Hospital of Patras, Greece
Third Department of Surgery, “ATTIKON” University General Hospital, Athens, Greece
Clinical, Experimental Surgery and Translational Research, Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation Academy of Athens, Greece

Gastroenterology Rev 2025; 20 (3): 294–304

DOI: https://doi.org/10.5114/pg.2025.154724

Online publish date: 2025/09/23

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Introduction
Toll-like receptors (TLRs) play a key role in activating the immune system response after liver injury.

Aim
This experimental study aimed to investigate the expression of TLRs and their connecting signaling molecules in liver regeneration.

Material and methods
Eighty C57BL/6J mice were divided into eight equal groups: four groups underwent partial hepatectomy (liver resection, LR), and four groups underwent an abdominal incision without hepatectomy (sham, Sh). One group of each type was sacrificed at 12 h (LR12 and Sh12), 24 h (LR24 and Sh24), 36 h (LR36 and Sh36), and 168 h (LR168 and Sh168). Histological and immunohistochemical analyses, blood tests, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed.

Results
The qRT-PCR tests indicated significant differences in all immune response proteins (TLR1, TLR2, TLR6, IRAK4, TIRAP, NF-kB, MYD88) between all LR and Sh groups. A progressive increase in the expression of TLRs was observed in the first three pairs, with stabilization of their expression in the last group. Histological examination of liver specimens revealed regeneration of liver tissue in the LR groups. Immunohistochemical analysis revealed increased expression of signaling proteins (TLR1, TLR2, MYD88, IRAK4, TIRAP, NF-kB) in the LR groups as compared to the control groups. White blood, red blood cell count and liver function tests were significantly different between LR and Sh groups.

Conclusions
TLR expression was significantly higher in mice that underwent partial hepatectomy than the controls. Further research is required to investigate their potential as therapeutic targets in the management of acute or chronic liver failure after partial hepatectomy.

keywords:

The role of Toll-like receptors in liver regeneration after partial hepatectomy

Spyridon Dritsas 1 , Maximos Frountzas 2 , Dimitrios Schizas 3 , Francesk Mulita 4 , Michalis Katsimpoulas 5 , Paraskevas Gkolfakis 6 , Irene Lidoriki 3 , Ioannis Karavokyros 3 , Elias Liolis 7 , Evangelos Missiakos 8 , Theodore Liakakos 3 , Alkistis Kapelouzou 9

experimental, mouse model, liver regeneration, hepatectomy, Toll-like receptors