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Liver inflammation and fibrosis
Open accessAbstract
Chronic liver inflammation leads to fibrosis and cirrhosis, which is the 12th leading cause of death in the United States. Hepatocyte steatosis is a component of metabolic syndrome and insulin resistance. Hepatic steatosis may be benign or progress to hepatocyte injury and the initiation of inflammation, which activates immune cells. While Kupffer cells are the resident macrophage in the liver, inflammatory cells such as infiltrating macrophages, T lymphocytes, neutrophils, and DCs all contribute to liver inflammation. The inflammatory cells activate hepatic stellate cells, which are the major source of myofibroblasts in the liver. Here we review the initiation of inflammation in the liver, the liver inflammatory cells, and their crosstalk with myofibroblasts.
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“A key event in liver fibrogenesis is the activation of quiescent HSCs, which differentiate into myofibroblasts and secrete large amounts of collagen and profibrosis factors.( 71 )”
From The Emerging Role of B Cells in the Pathogenesis of NAFLD (2021) · cites this paper as [71]
Experimental — accuracy not yet measuredIn the citing paper
“A key event in liver fibrogenesis is the activation of quiescent HSCs, which differentiate into myofibroblasts and secrete large amounts of collagen and profibrosis factors.( 71 )”
From The Emerging Role of B Cells in the Pathogenesis of NAFLD (2021) · cites this paper as [71]
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“Hepatic stellate cells (HSCs) play pivotal roles in the pathological development of liver fibrosis27.”
From SUMOylation inhibitors synergize with FXR agonists in combating liver fibrosis (2020) · cites this paper as [27]
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The Emerging Role of B Cells in the Pathogenesis of NAFLD
Barrow, F., Khan, S., Wang, H., & Revelo, X. S. (2021) · Hepatology · doi:10.1002/hep.31889 · Cited by 126
Cirrhosis: A Questioned Risk Factor for Hepatocellular Carcinoma
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“Examples are the influence of PPAR agonists on lipid metabolism, the increase of bile flow, or the immunosuppressive effects of ursodeoxycholic acid (UDCA) (Koyama and Brenner 2017; Li et al.”
BackgroundThe role of cGAS-STING signalling in liver diseases
Chen, R., Du, J., Zhu, H., & Ling, Q. (2021) · JHEP Reports · doi:10.1016/j.jhepr.2021.100324 · Cited by 131
Sarcopenia in chronic liver disease: mechanisms and countermeasures
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“Infiltrating macrophages, T lymphocytes, neutrophils, and DCs are examples of the inflammatory cells in the liver that cause inflammation (11).”
BackgroundCrocin: A fighter against inflammation and pain
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Crosstalk Between Liver Macrophages and Surrounding Cells in Nonalcoholic Steatohepatitis
Li, H., Zhou, Y., Wang, H., Zhang, M., Qiu, P., Zhang, M., Zhang, R., Zhao, Q., & Liu, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01169 · Cited by 117
“In response to lipopolysaccharide (LPS), HSCs secreted intercellular adhesion molecule-1 (ICAM1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin to induce KC migration (74).”
BackgroundTargeting CSF-1R represents an effective strategy in modulating inflammatory diseases
Xiang, C., Li, H., & Tang, W. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106566 · Cited by 114
MyD88 in hepatic stellate cells enhances liver fibrosis via promoting macrophage M1 polarization
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“Immune cells, including macrophages, play a key role in the process of liver injury and subsequent liver fibrosis [1, 8, 9].”
Mesenchymal stem cells in fibrotic diseases—the two sides of the same coin
Qin, L., Liu, N., Bao, C.-L.-M., Yang, D.-Z., Ma, G.-X., Yi, W.-H., Xiao, G.-Z., & Cao, H.-L. (2023) · Acta Pharmacologica Sinica · doi:10.1038/s41401-022-00952-0 · Cited by 114
“, NLRP3) and proinflammatory cytokine production, which activates HSCs and produces ECM leading to fibrosis [175, 176].”
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Organ and brain crosstalk: The liver-brain axis in gastrointestinal, liver, and pancreatic diseases
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ROS/RNS as molecular signatures of chronic liver diseases
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“Similar to humans, HCC development in Sod1KO mice progresses from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) with fibrosis, which eventually progresses to HCC. Oxidative stress plays a role in NAFLD to NASH progression, and liver inflammation is the main mechanism that drives the…”
BackgroundInfluentialMacrophage in liver Fibrosis: Identities and mechanisms
Wang, Z., Du, K., Jin, N., Tang, B., & Zhang, W. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.110357 · Cited by 119
Kupffer-derived matrix metalloproteinase-9 contributes to liver fibrosis resolution
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“Immune cells and inflammatory factors cooperate in the establishment and resolution of liver fibrosis [4, 5].”
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“Consistent with the bidirectional interaction between activated HSCs and immune cells in CLD, HSC activation and survival are regulated by specific mediators secreted from macrophages, T cells and regulatory T cells, including IL-1β, TNF and amphiregulin 13,14,228,229 .”
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The innate immune receptor TREM-1 promotes liver injury and fibrosis
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“Hepatic fibrosis occurs in association with chronic liver injury and hepatocellular death caused by, among others, viral hepatitis, alcohol abuse, and drugs or chemical insults (1–6).”
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“Persistent inflammation leads to hepatocyte injury, activation of fibrogenic pathways and extra-cellular matrix deposition, ultimately resulting in fibrosis and cirrhosis [107].”
Metabolic inflammation as an instigator of fibrosis during non-alcoholic fatty liver disease
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Animal and Organoid Models of Liver Fibrosis
Bao, Y., Wang, L., Pan, H., Zhang, T.-R., Chen, Y., Xu, S.-J., Mao, X., & Li, S.-W. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.666138 · Cited by 101
“The collected inflammatory cells further activate effector cells, which promote fibrosis (Hernandez-Gea and Friedman, 2011; Koyama and Brenner, 2017; Parola and Pinzani, 2019).”
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Metadata
- Authors
- Koyama, Y., & Brenner, D. A.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Brenner, David A.
- Venue
- Journal of Clinical Investigation
- Published
- 2017-01-03
- Volume
- 127
- Issue
- 1
- Pages
- 55-64
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- PMC
- PMC5199698
- OpenAlex
- W2562949639
- Cited by
- 1,295
- References
- 158
- Citations by year
- 2026: 139 · 2025: 162 · 2024: 159 · 2023: 171 · 2022: 173 · 2021: 177 · 2020: 151 · 2019: 85 · 2018: 63 · 2017: 13
- FWCI
- 12.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (ES010337, AA011999)
- National Institute on Alcohol Abuse and Alcoholism (U01AA021856, P50AA011999)
- National Institute of Environmental Health Sciences (P42ES010337)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- liver inflammation, liver fibrosis, liver cirrhosis, hepatic steatosis, Kupffer cells, hepatic stellate cells, myofibroblasts, immune cell crosstalk, T cells, neutrophils, dendritic cells, metabolic syndrome, insulin resistance
- MeSH terms
- Animals, Dendritic Cells, Hepatitis, Humans, Inflammation, Kupffer Cells, Liver, Liver Cirrhosis, Neutrophils, T-Lymphocytes, Hepatic Stellate Cells, Myofibroblasts
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