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NF-κB in the liver—linking injury, fibrosis and hepatocellular carcinoma
Open accessAbstract
Hepatic cirrhosis and hepatocellular carcinoma (HCC) are the most common causes of death in patients with chronic liver disease. Chronic liver injury of virtually any etiology triggers inflammatory and wound-healing responses that in the long run promote the development of hepatic fibrosis and HCC. Here, we review the role of the transcription factor nuclear factor-κB (NF-κB), a master regulator of inflammation and cell death, in the development of hepatocellular injury, liver fibrosis and HCC, with a particular focus on the role of NF-κB in different cellular compartments of the liver. We propose that NF-κB acts as a central link between hepatic injury, fibrosis and HCC, and that it may represent a target for the prevention or treatment of liver fibrosis and HCC. However, NF-κB acts as a two-edged sword and inhibition of NF-κB may not only exert beneficial effects but also negatively impact hepatocyte viability, especially when NF-κB inhibition is pronounced. Finding appropriate targets or identifying drugs that either exert only a moderate effect on NF-κB activity or that can be specifically delivered to nonparenchymal cells will be essential to avoid the increase in liver injury associated with complete NF-κB blockade in hepatocytes.
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“However, the decisive factor is that NF-κB-activation additionally causes a significantly increased resistance against apoptosis in aHSCs.[21]”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [21]
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Metadata
- Authors
- Luedde, T., & Schwabe, R. F.
- Affiliations
- Universitätsklinikum Aachen (DE)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Luedde, Tom
- Schwabe, Robert F.
- Venue
- Nature Reviews Gastroenterology & Hepatology
- Published
- 2011-02
- Volume
- 8
- Issue
- 2
- Pages
- 108-118
- ISSN
- 1759-5045 (ISSN-L)
- 1759-5053
- PMC
- PMC3295539
- OpenAlex
- W1976777085
- Cited by
- 1,345
- References
- 137
- Citations by year
- 2026: 97 · 2025: 99 · 2024: 119 · 2023: 109 · 2022: 122 · 2021: 156 · 2020: 120 · 2019: 95 · 2018: 79 · 2017: 76 · 2016: 66 · 2015: 68 · 2014: 51 · 2013: 38 · 2012: 42
- FWCI
- 5.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Gastroenterology & Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5u54ca126513-03)
- National Institute on Alcohol Abuse and Alcoholism (R01AA020211)
- National Cancer Institute (U54 CA126513.)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK076920)
- National Center for Complementary and Integrative Health (R21AT003878)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Keywords
- NF-κB, liver fibrosis, hepatocellular carcinoma, chronic liver disease, liver cirrhosis, chronic liver injury, liver inflammation, hepatocytes, non-parenchymal liver cells, NF-κB inhibition, hepatocyte viability
- MeSH terms
- Cell Survival, Fibrosis, Carcinoma, Hepatocellular, Homeostasis, Humans, Liver, Liver Neoplasms, NF-kappa B, Hepatocytes
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