The aryl hydrocarbon receptor in liver injury: a double-edged sword in roles, mechanisms, and future perspectives

The aryl hydrocarbon receptor (AhR) is a key regulatory factor that enables the organism to sense and integrate environmental and metabolic signals. Its biological function exhibits a universal "dual nature," a feature that has been relatively well studied in organs such as the skin, lungs, and intestines. However, in the pathological processes of the liver-the central metabolic organ-the specific molecular mechanisms and regulatory networks that determine the functional orientation of AhR (whether protective or detrimental) remain a frontier and highly controversial area of research. This review aims to critically synthesize existing evidence, elucidating how AhR influences the progression of liver injury by regulating apoptosis, stress-induced damage, metabolic homeostasis, autophagy, fibrosis, and tumor development. It further explores the causes of its functional heterogeneity, such as ligand specificity and tissue microenvironment. By analyzing current controversies and cognitive gaps in the field, this article seeks to provide a framework for clarifying the complex role of AhR in liver diseases and to guide future exploration of targeted intervention strategies.

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Publication Details

Journal
Frontiers in Pharmacology
Published
2026-01-08
DOI
https://doi.org/10.3389/fphar.2025.1720827
Citations
1
Primary Topic
Toxic Organic Pollutants Impact
Type
article
Field-Weighted Citation Impact
31.09
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The aryl hydrocarbon receptor in liver injury: a double-edged sword in roles, mechanisms, and future perspectives

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1 citations
Frontiers in Pharmacology
Toxic Organic Pollutants Impact
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article

The aryl hydrocarbon receptor in liver injury: a double-edged sword in roles, mechanisms, and future perspectives

Shuangxing Li, Y. Fred Yang, Yanru Wang, Xingchao Geng, Chao Wang, Yikun Zhang, Tianqi Ren
article en
1 citations

Abstract

The aryl hydrocarbon receptor (AhR) is a key regulatory factor that enables the organism to sense and integrate environmental and metabolic signals. Its biological function exhibits a universal "dual nature," a feature that has been relatively well studied in organs such as the skin, lungs, and intestines. However, in the pathological processes of the liver-the central metabolic organ-the specific molecular mechanisms and regulatory networks that determine the functional orientation of AhR (whether protective or detrimental) remain a frontier and highly controversial area of research. This review aims to critically synthesize existing evidence, elucidating how AhR influences the progression of liver injury by regulating apoptosis, stress-induced damage, metabolic homeostasis, autophagy, fibrosis, and tumor development. It further explores the causes of its functional heterogeneity, such as ligand specificity and tissue microenvironment. By analyzing current controversies and cognitive gaps in the field, this article seeks to provide a framework for clarifying the complex role of AhR in liver diseases and to guide future exploration of targeted intervention strategies.

Frontiers in PharmacologyVol. 16
China Pharmaceutical University (CN), National Institutes for Food and Drug Control (CN)
Openalex Percentile: Top 2%
Toxic Organic Pollutants Impact
31.09
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