ROS/RNS as molecular signatures of chronic liver diseases
Abstract
The liver can succumb to oxidant damage during the development of chronic liver diseases. Despite their physiological relevance to hepatic homeostasis, excessive reactive oxygen/nitrogen species (ROS/RNS) production under pathological conditions is detrimental to all liver constituents. Chronic oxidative stress coupled to unresolved inflammation sets in motion the activation of profibrogenic hepatic stellate cells (HSCs) and later pathogenesis of liver fibrosis, cirrhosis, and liver cancer. The liver antioxidant and repair systems, along with autophagic and ferroptotic machineries, are implicated in the onset and trajectory of disease development. In this review, we discuss the ROS/RNS-related mechanisms underlying liver fibrosis of distinct etiologies and highlight preclinical and clinical trials of antifibrotic therapies premised on remediating oxidative/nitrosative stress in hepatocytes or targeting HSC activation.
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HSCs are activated by inflammatory cytokines, ROS, and apoptotic bodies from dying hepatocytes, and upon activation transdifferentiate into myofibroblast-like cells producing excessive ECM components including collagen I and III.
“Concomitant with immune activation, hepatic stellate cells (HSCs), the primary fibrogenic cell type in the liver, are activated by inflammatory cytokines, reactive oxygen species, and apoptotic bodies from dying hepatocytes (Che et al. 2023; Kim et al. 2025). Upon activation, HSCs transdifferentiate into myofibroblast-like cells expressing α-smooth muscle actin and produce excessive extracellular”
From The double-edged sword of regulatory T cells in MASLD: from inflammation control to fibrosis promotion (2026) · cites this paper as Che et al. 2023
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References 119 · Cited by 110
- Authors
- Che, Z., Zhou, Z., Li, S.-Q., Gao, L., Xiao, J., & Wong, N.-K.
- Affiliations
- First Affiliated Hospital of Jinan University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Southern Medical University (CN)
- Shantou University (CN)
- Corresponding author
- Xiao, Jia
- Wong, Nai-Kei
- Venue
- Trends in Molecular Medicine
- Publisher
- Elsevier BV
- Published
- 2023-11
- Volume
- 29
- Issue
- 11
- Pages
- 951-967
- ISSN
- 1471-4914 (ISSN-L)
- OpenAlex
- W4386607511
- Cited by
- 110
- References
- 119
- Citations by year
- 2026: 40 · 2025: 41 · 2024: 29
- FWCI
- 4.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Trends in Molecular Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Li Ka Shing Foundation
- National Natural Science Foundation of China (22107045, 32073002, 82122009)
- Shantou University Medical College (510858044)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- reactive oxygen species, reactive nitrogen species, chronic liver disease, oxidative stress, nitrosative stress, liver fibrosis, hepatic stellate cells, liver cirrhosis, liver cancer, ferroptosis, autophagy, antioxidant defense, antifibrotic therapy, inflammation
- MeSH terms
- Animals, Chronic Disease, Humans, Liver Cirrhosis, Liver Diseases, Reactive Oxygen Species, Oxidative Stress, Reactive Nitrogen Species, Hepatic Stellate Cells
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