Metalloproteinases and their inhibitors: Regulators of wound healing
Open accessAbstract
Wound healing is a dynamic process that involves a coordinated response of many cell types representing distinct tissue compartments and is fundamentally similar among tissue types. Among the many gene products that are essential for restoration of normal tissue architecture, several members of the matrix metalloproteinase (MMP) family function as positive and, at times, negative regulators of repair processes. MMPs were initially thought to only function in the resolution phase of wound healing, particularly during scar resorption; however, recent evidence suggests that they also influence other wound-healing responses, such as inflammation and re-epithelialization. In this review, we discuss what is currently known about the function of MMPs in wound healing and will provide suggestions for future research directions.
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The remodeling phase begins after deposition of significant ECM (mainly collagens I and III) and is characterized by MMP- and TIMP-mediated degradation and remodeling of new collagen, generally resulting in scar tissue formation or maturation.
“Following the deposition of significant amounts of ECM (predominantly collagens type I and III) during the proliferative phase, the remodeling phase of wound healing begins. This phase is characterized by MMP- and tissue inhibitor of metalloproteinase (TIMP)-mediated degradation and remodeling of the newly deposited collagen, generally resulting in scar tissue formation/maturation [86,100].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [100]
Elevation of TNFα leads to decreased production of granulation tissue, whereas low doses of TNFα promote collagen disposition.
“Elevation of TNFα leads to decreased production of granulation tissue, whereas low doses of TNFα promote collagen disposition,58–61 demonstrating the importance of accurate cytokine regulation during wound healing.”
From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [58]
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- Authors
- Gill, S. E., & Parks, W. C.
- Affiliations
- University of Washington (US)
- Corresponding author
- Gill, Sean E.
- ORCID
- Gill, Sean E.
- Venue
- The International Journal of Biochemistry & Cell Biology
- Publisher
- Elsevier BV
- Published
- 2008-06
- Volume
- 40
- Issue
- 6-7
- Pages
- 1334-1347
- ISSN
- 1357-2725 (ISSN-L)
- PMC
- PMC2746915
- OpenAlex
- W1997830990
- Cited by
- 742
- References
- 4
- Citations by year
- 2026: 26 · 2025: 20 · 2024: 34 · 2023: 38 · 2022: 33 · 2021: 50 · 2020: 43 · 2019: 36 · 2018: 41 · 2017: 54 · 2016: 55 · 2015: 36 · 2014: 54 · 2013: 45 · 2012: 43
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The International Journal of Biochemistry & Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL089455, R01HL082658)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- matrix metalloproteinases, matrix metalloproteinase inhibitors, wound healing, inflammation, re-epithelialization, extracellular matrix remodeling, tissue repair
- MeSH terms
- Animals, Humans, Models, Biological, Wound Healing, Gene Expression Regulation, Enzymologic, Tissue Inhibitor of Metalloproteinases, Metalloproteases
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