PhD Scientific Days 2026

Poster Session 1.A - Molecular Medicine

Hepatocyte-Specific Deletion of De Novo DNA Methyltransferase 3a and 3b Leads to Early Adaptive Response to Acetaminophen-Induced Liver Injury in Mice

Előadó neve

Muazu, Muhyiddeen

Neptune code

CSZ35K

Előadó munkahelye

Semmelweis University, Department of Molecular Biology

Előadó telefonszáma

+36706587342

Előadó e-mail címe

muhyiddeen.muazu@phd.semmelweis.hu

Az előadás címe

Hepatocyte-Specific Deletion of De Novo DNA Methyltransferase 3a and 3b Leads to Early Adaptive Response to Acetaminophen-Induced Liver Injury in Mice

Szerző(k) neve és munkahelye

Muhyiddeen Muazu¹, Daniel Marton Toth¹, Virgil Tamatey^1,2, Bence Blaha¹, Diya Alex¹, Katalin Dezso³, Flora Szeri², Tamas Aranyi^1,2

1: Semmelweis University, Department of Molecular Biology
2: HUN-REN Research Center for Natural Sciences, Institute of Molecular Life Sciences
3: Semmelweis University, Department of Pathology and Experimental Cancer Research

Bemutatás módja

Poszter

Szekció

Poster Session 1.A - Molecular Medicine

Language of the presentation

English

Preferred session

Molecular Medicine

Összefoglaló szövege

Introduction
Acetaminophen (APAP) overdose has been shown to account for 70% of all acute liver failure cases in Europe. At therapeutic doses, around 90% of APAP is metabolised by sulfation and glucuronidation. 10% is converted to the toxic N-acetyl-p-benzoquinone imine (NAPQI) by CYP enzymes, which is eliminated through glutathione conjugation. APAP exposure was reported to cause changes in DNA methylation patterns in the liver. However, the exact role of DNA methyltransferases in APAP-induced liver injury (AILI) remains unclear.

Aims
This work aims to determine the function of Dnmt3a and Dnmt3b de novo DNA methyltransferases in AILI using Alfp-CreTg/Tg/Dnm3afl/fl/Dnmt3bfl/fl Double knockout (DKO) mice.

Methods
The DKO mice were generated by breeding Alfp-CreTg/-/Dnmt3afl/fl/3bfl/fl animals. Male mice (8 weeks old) were treated with 300mg/kg APAP or saline. Animals were sacrificed at 6h or 24h, and the liver and serum were collected. Gene expression changes of APAP metabolism-related pathways were analyzed by real-time PCR.

Result
The DKO mice were viable and showed no phenotype. Cre expression was detected at E13.5 embryonic day, and a significantly decreased expression of Dnnmt3a and Dnmt3b was observed in DKO mice from E18.5. In contrast, AILI in adult mice leads to upregulation of Dnmt3a and Dnmt3b at 6h in Wild-Type (WT), indicating the participation of de novo DNA methylation in AILI. Sult1a1, Cyp1a2, and Cyp3a11 were downregulated earlier in the DKO group than in the WT group. The NADPH quinone oxidoreductase (Nqo1) gene, which plays a protective role against energy depletion caused by APAP and can also convert NAPQI to APAP for detoxification by sulfation & glucuronidation, was upregulated only in the DKO group. Glutathione-related genes Gclc, Gsta1, and Gstp1 were upregulated independent of the genotype. The small heterodimer protein (Shp), whose deletion has been shown to protect mice against AILI, was downregulated only in the DKO group.

Conclusion
These results reveal a novel DNA methylation-dependent regulatory mechanism in the AILI response, indicating that Dnmt3a and Dnmt3b are promising targets for limiting early disease progression.

Funding
NKFIH K132695, Advanced-152689, Stipendium Hungaricum PhD Fellowship, SE250+ 2025/26/1.

University

Semmelweis University

Supervisor

Tamas Aranyi MD PhD

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

in doctoral studies after complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

9753

Start

17:36

End

17:39