The role of matrix metalloproteinases in liver function and disease
Open accessAbstract
Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) play critical roles in the pathogenesis of liver diseases, particularly in conditions such as fibrosis, cirrhosis, and liver cancer. This review highlights the diagnostic and prognostic potential of MMPs, emphasizing their involvement in metastasis, de-differentiation, and hepatic cell proliferation. Utilizing advanced reporter mouse models has proven instrumental in assessing intraglandular MMP activity and predicting metastatic risks, paving the way for targeted therapeutic interventions. Current research indicates that specific MMPs and TIMPs can serve as valuable biomarkers for liver function and disease progression, although a clear consensus on their clinical utility remains elusive. Ongoing studies explore MMP-targeted therapies with potential applications in liver disease management, particularly in reducing fibrosis and enhancing liver regeneration. Future directions in this field involve elucidating the roles of MMPs in ischemia and transplantation, with the aim of improving clinical outcomes. Emerging therapeutic strategies focus on achieving a balance between MMP activity and TIMP expression to optimize liver function, highlighting the need for organ-specific targeting. Overall, this comprehensive overview underscores the importance of MMPs and TIMPs in liver function and liver disease, as well as the necessity for further research to harness their potential in clinical practice.
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Both TIMPs and MMPs can be secreted by macrophages and aHSCs.
“Both TIMPs and MMPs can be secreted by macrophages and aHSCs (80, 81).”
From Targeting macrophages in liver fibrosis (2026) · cites this paper as [80]
TIMP-1 not only inhibits collagen degradation by suppressing MMP activity but also promotes survival and proliferation of aHSCs, perpetuating and amplifying the fibrotic response.
“TIMP-1 not only inhibits collagen degradation by suppressing MMP activity but also promotes survival and proliferation of aHSCs, perpetuating and amplifying the fibrotic response (80, 83).”
From Targeting macrophages in liver fibrosis (2026) · cites this paper as [80]
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Targeting macrophages in liver fibrosis
González del Barrio, L., Ipsen, D. H., Pfister, D. R., Hancz, D., & Scott, C. L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1835489 · Cited by 3 · see citing works
“Both TIMPs and MMPs can be secreted by macrophages and aHSCs (80, 81).”
- Authors
- Mitropoulou, G., Kompoura, V., Saffioti, F., & Mavroeidis, V. K.
- Affiliations
- Democritus University of Thrace (GR)
- University of Messina (IT)
- North Bristol NHS Trust (GB)
- Corresponding author
- Mavroeidis, Vasileios K.
- Venue
- Frontiers in Bioscience-Landmark
- Publisher
- IMR Press
- Published
- 2025-05-20
- Volume
- 30
- Issue
- 5
- Pages
- 27127-27127
- ISSN
- 2768-6698 (ISSN-L)
- 2768-6701
- OpenAlex
- W4411028882
- Cited by
- 14
- References
- 7
- Citations by year
- 2026: 10 · 2025: 4
- FWCI
- 1.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Bioscience-Landmark (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
- Keywords
- matrix metalloproteinases, tissue inhibitors of metalloproteinases, liver fibrosis, liver cirrhosis, hepatocellular carcinoma, liver cancer metastasis, liver regeneration, biomarkers, liver transplantation, hepatic ischemia, hepatocyte proliferation
- MeSH terms
- Animals, Humans, Liver, Liver Cirrhosis, Liver Diseases, Liver Neoplasms, Biomarkers, Tissue Inhibitor of Metalloproteinases, Matrix Metalloproteinases
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