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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]
In 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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“Accordingly, Tc-cAbVCAM1-5 signal quantification had a strong diagnostic power to detect any degree of inflammation (histological score [1–3]) or moderate-to-severe inflammation (histological score [2-3]), returning respective areas under the curves (AUCs) of 0.”
BackgroundOxidative Stress in Chronic Liver Disease and Portal Hypertension: Potential of DHA as Nutraceutical
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“M2-macrophages, n the other hand, secrete anti-inflammatory cytokines and growth factors, such as IL-10, transforming growth factor-β (TGF-β), platelet derived growth factor (PDGF) and epidermal growth factor (EGF), and participate in wound healing [12,36,37].”
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“Studies in mouse models show that this leads to increased infiltration of macrophages and T cells, further enhancing the local inflammatory response [39,40].”
The emerging role of tissue regulatory T cells in tissue repair and regeneration
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“HSC proliferation and differentiation are mainly induced by TGF-β1, Platelet-derived growth factor-B (PDGF-B), and Angiotensin II [42,43], but reactive oxygen species (ROS) produced by neutrophils also play a major role in the process [44,45].”
BackgroundExploring the Complex Role of Coagulation Factor VIII in Chronic Liver Disease
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“Patients with hemophilia infected with human immunodeficiency virus (HIV) and HCV after treatment with a contaminated FVIII concentrate frequently developed cirrhosis and HCC.96,97 Although HCV infection is not known to induce the development of FVIII inhibitors,98 some patients with HCV–HIV co-infection showed decrea…”
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“It has been suggested that macrophages are the major source responsible for hepatic inflammation whereas hepatic stellate cells are mainly responsible for hepatic fibrosis (Kinoshita et al., 2010; Yukinori & David, 2017).”
BackgroundGrewal, T., & Buechler, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031070 · Cited by 27
“While the abovementioned studies examined the potential contribution of PCSK9 to the severity and progression of inflammation, several reports suggest PCSK9 to contribute to the early steps of hepatic inflammation, which is the main driver of liver injury and leads to liver fibrosis and cirrhosis [97].”
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“DISCUSSION Liver fibrosis/cirrhosis is characterized by a complex inflammatory response with tightly regulated interactions between damaged hepatocytes and recruited immune cells [21, 22].”
BackgroundA Healthful Plant-Based Diet Is Associated with Lower Odds of Nonalcoholic Fatty Liver Disease
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“aggravates inflammatory responses (45).”
Tanshinone IIA and hepatocellular carcinoma: A potential therapeutic drug
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“Even oxidative stress plays an important role in the pathophysiological changes that progress to cirrhosis and eventually to hepatocellular carcinoma (HCC) (51, 52).”
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“The DAMPs released from damaged hepatocytes can activate KCs and promote circulating macrophage infiltration in the liver (12).”
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BRD4: an effective target for organ fibrosis
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“Chronic alcoholic liver disease, inflammation, hepatitis viral infection, cholestasis and many other diseases that cause liver injury can induce hepatic fibrosis [69, 199, 200].”
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“More recently, the definition of M1 and M2 cells has been questioned [8,19,35].”
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A 3D Human Liver Model of Nonalcoholic Steatohepatitis
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“An increase of CXCL8 and CXCL10 was also observed in the 3D liver NASH model, confirming the induction of an inflammatory environment, which is a key characteristic of NASH disease.(31) As previously described, CXCL8 could be a marker of NASH combined with diabetes.”
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Histone deacetylase inhibitor givinostat attenuates nonalcoholic steatohepatitis and liver fibrosis
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Down-Regulation of CXXC5 De-Represses MYCL1 to Promote Hepatic Stellate Cell Activation
Wu, X., Dong, W., Kong, M., Ren, H., Wang, J., Shang, L., Zhu, Z., Zhu, W., & Shi, X. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.680344 · Cited by 26
“Once activated, HSCs trans-differentiate into myofibroblasts characteristically expressing smooth muscle actin (α-SMA) and periostin (Koyama and Brenner, 2017).”
Background
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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