MMP-8 Is the Predominant Collagenase in Healing Wounds and Nonhealing Ulcers
Abstract
Background The initial cleavage of collagen by collagenase represents the rate-limiting step in the degradation of this central extracellular matrix protein. Chronic nonhealing ulcers, especially pressure ulcers, typically contain elevated levels of collagenolytic activity. However, there have been no detailed attempts to identify the source of these collagenases and their activity either in normal healing wounds or in chronic nonhealing ulcers.Materials and methods Levels of the matrix metalloproteinases, MMP-1 and MMP-8, and the tissue inhibitor of matrix metalloproteinases, TIMP-1, were measured in fluids and tissues of healing human wounds and nonhealing ulcers by ELISA. Relative MMP-1 and MMP-8 levels were also analyzed by substrate preference in a functional assay.Results The patterns of the collagenases MMP-1 and MMP-8 in healing wounds were distinct, with MMP-8 appearing in significantly greater amounts than MMP-1. Chronic nonhealing ulcers were characterized by significantly higher levels of MMP-1 and MMP-8, and lower levels of TIMP-1, than in healing wounds. Levels of both MMP-1 and MMP-8 varied greatly in chronic ulcers, although MMP-8 was always the predominant collagenase present in these wounds. Interestingly, these collagenases were present almost exclusively in their inactive forms in healing wounds, whereas nonhealing ulcers possessed significant levels of the active forms of these enzymes.Conclusions These results clearly demonstrate that the neutrophil-derived MMP-8 is the predominant collagenase present in normal healing wounds and suggest that overexpression and activation of this collagenase may be involved in the pathogenesis of nonhealing chronic ulcers. In addition, excessive collagenolytic activity in chronic ulcers is made possible, partly because of the reduced levels of the inhibitor, TIMP-1.
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MMP-1 and MMP-8 are important, as they have been found to be active during wound healing and remodeling.
“Specifically, MMP‐1 and MMP‐8 are important, as they have been found to be active during wound healing and remodeling.”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [257]
MMP-1 is more proficient in cleavage of collagen type III, while MMP-8 is more efficient in degrading collagen type I and is the main collagenase active in regular healing.
“Both are used in the cleavage of collagen, with MMP‐1 being more proficient in the cleavage of collagen type III, while MMP‐8 is more efficient in degrading collagen type I and is the main collagenase active in regular healing.”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [257]
Neutrophil-derived proteases such as elastase and matrix metalloproteinases can degrade healthy extracellular matrix, and increased levels of these proteases have been repeatedly detected in chronic wounds.
“neutrophil-derived proteases, such as elastase and matrix metalloproteinases (MMPs), can degrade healthy extracellular matrix (ECM), and increased levels of these proteases have been repeatedly detected in chronic wounds [52–56].”
From Immunology of Wound Healing (2018) · cites this paper as [55]
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“In humans, MMP-8 is 100-fold increased in chronic wound fluids compared with acute wounds, although the implication of this is still unknown.(11) MMP-26 (matrilysin-2) is abundantly expressed in the human placenta, uterus,(12,13) endometrial glandular cells,(14) kidney,(15) the gastrointestinal tract,(16) and epitheli…”
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CONSEQUENCES OF LONG-TERM INFLAMMATION
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Exosomal miRNA-26b-5p from PRP suppresses NETs by targeting MMP-8 to promote diabetic wound healing
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“Collagenases such as MMP-1 and MMP-8 are commonly detected in healing wounds [12].”
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Metalloproteinases in chronic and acute wounds: A systematic review and meta‐analysis
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- Authors
- Nwomeh, B. C., Liang, H.-X., Cohen, I. K., & Yager, D. R.
- Affiliations
- Virginia Commonwealth University (US)
- ORCID
- Nwomeh, Benedict C.
- Venue
- Journal of Surgical Research
- Publisher
- Elsevier BV
- Published
- 1999-02
- Volume
- 81
- Issue
- 2
- Pages
- 189-195
- ISSN
- 0022-4804 (ISSN-L)
- OpenAlex
- W1988325190
- Cited by
- 357
- References
- 0
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 14 · 2023: 8 · 2022: 8 · 2021: 11 · 2020: 13 · 2019: 10 · 2018: 18 · 2017: 18 · 2016: 18 · 2015: 14 · 2014: 9 · 2013: 15 · 2012: 20
- FWCI
- 12.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Surgical Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM20298)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pineapple and bromelain studies
- Keywords
- MMP-8, MMP-1, TIMP-1, collagenase, wound healing, chronic non-healing ulcers, pressure ulcers, collagen degradation, extracellular matrix, neutrophils, matrix metalloproteinases, collagenolytic activity
- MeSH terms
- Adult, Chronic Disease, Pressure Ulcer, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Mastectomy, Middle Aged, Skin, Surgical Flaps, Time Factors, Varicose Ulcer, Wound Healing, Wounds and Injuries, Collagenases, Tissue Inhibitor of Metalloproteinase-1, Matrix Metalloproteinase 1, Matrix Metalloproteinase 8
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