Hepatic Stellate Cell-Macrophage Crosstalk in Liver Fibrosis and Carcinogenesis
Open accessAbstract
Chronic liver injury due to viral hepatitis, alcohol abuse, and metabolic disorders is a worldwide health concern. Insufficient treatment of chronic liver injury leads to fibrosis, causing liver dysfunction and carcinogenesis. Most cases of hepatocellular carcinoma (HCC) develop in the fibrotic liver. Pathological features of liver fibrosis include extracellular matrix (ECM) accumulation, mesenchymal cell activation, immune deregulation, and angiogenesis, all of which contribute to the precancerous environment, supporting tumor development. Among liver cells, hepatic stellate cells (HSCs) and macrophages play critical roles in fibrosis and HCC. These two cell types interplay and remodel the ECM and immune microenvironment in the fibrotic liver. Once HCC develops, HCC-derived factors influence HSCs and macrophages to switch to protumorigenic cell populations, cancer-associated fibroblasts and tumor-associated macrophages, respectively. This review aims to summarize currently available data on the roles of HSCs and macrophages in liver fibrosis and HCC, with a focus on their interaction.
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Macrophages are the main cellular source of potent pro-fibrogenic signals including TGFβ, PDGF, TNF, and IL-1β, and also secrete MMPs that activate latent TGFβ stored in the ECM.
“Macrophages are the main cellular source of potent pro-fibrogenic signals including TGFβ, PDGF, TNF, and IL-1β, and also secrete matrix metalloproteinases (MMPs) that activate latent TGFβ stored in the ECM (24, 55).”
From Hepatic Stellate Cell-Immune Interactions in NASH (2022) · cites this paper as [55]
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References 172 · Cited by 189
- Authors
- Matsuda, M., & Seki, E.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Corresponding author
- Seki, Ekihiro
- Venue
- Seminars in Liver Disease
- Publisher
- Georg Thieme Verlag KG
- Published
- 2020-04-02
- Volume
- 40
- Issue
- 03
- Pages
- 307-320
- ISSN
- 0272-8087 (ISSN-L)
- 1098-8971
- PMC
- PMC7484001
- OpenAlex
- W3014902879
- Cited by
- 189
- References
- 172
- Citations by year
- 2026: 36 · 2025: 50 · 2024: 28 · 2023: 44 · 2022: 20 · 2021: 8 · 2020: 3
- FWCI
- 2.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Seminars in Liver Disease (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (R01AA027036, R01DK085252, R21AA025841, P01CA233452)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- hepatic stellate cells, hepatic macrophages, liver fibrosis, hepatocellular carcinoma, tumor-associated macrophages, cancer-associated fibroblasts, extracellular matrix remodeling, tumor microenvironment, chronic liver injury
- MeSH terms
- Animals, Cell Communication, Carcinoma, Hepatocellular, Humans, Kupffer Cells, Liver Cirrhosis, Liver Neoplasms, Hepatic Stellate Cells, Tumor Microenvironment, Carcinogenesis
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