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MMP generated matrikines
Open accessAbstract
Matrikines originate from the fragmentation of extracellular matrix proteins and regulate cellular activities by interacting with specific receptors. Matrikines are implicated in inflammation, immune responses, organ development, wound repair, angiogenesis, atherosclerosis, tumor progression and metastasis due to their ability to alter cellular migration, chemotaxis, and mitogenesis. Matrix metalloproteinases (MMPs) degrade extracellular matrix components under normal circumstances and in disease processes. Of the 20 MMPs identified, MMP-1, MMP-2, MMP-8, MMP-9, and MMP-12 have been implicated in regulating the matrikines Val-Gly-Val-Ala-Pro-Gly (elastin peptide) and proline-glycine-proline (PGP). Elastin peptide fragments are generated by elastolytic enzymes and have implications in atherosclerosis, neovascularization, chronic obstructive pulmonary disease, skin disease, as well as tumor invasion and spread. PGP is produced through a multistep pathway that liberates the tripeptide fragment from extracellular collagen. PGP is best described for its role in neutrophil chemotaxis and is implicated in the pathogenesis of corneal ulcers and in chronic lung conditions. In chronic cigarette smoke related lung disease, the PGP pathway can become a self-propagating cycle of inflammation through cigarette-smoke mediated inhibition of leukotriene A4 hydrolase, the enzyme responsible for degrading PGP and halting acute inflammation. This review highlights the roles of MMPs in generating these important matrikines.
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“Unrestricted release of PGP motives in the transplantation of organs such as heart and lung mediate chronic inflammation and rejection [102, 103].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [102]
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“MMPs per se degrade collagens and expose cryptic three-peptide motives PGP (Pro-Gly-Pro), which trigger CXCR2 receptors of neutrophils and orchestrate their chemotaxis and interplay with adaptive immunity.”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [102]
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“Besides, some cryptic laminin motives induce macrophage and neutrophil chemotaxis and upregulate MMPs activity [102].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [102]
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Metadata
- Authors
- Wells, J. M., Gaggar, A., & Blalock, J. E.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Wells, J. Michael
- Venue
- Matrix Biology
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 44-46
- Pages
- 122-129
- ISSN
- 0945-053X (ISSN-L)
- PMC
- PMC4838901
- OpenAlex
- W2035683946
- Cited by
- 263
- References
- 75
- Citations by year
- 2026: 19 · 2025: 15 · 2024: 25 · 2023: 35 · 2022: 15 · 2021: 30 · 2020: 33 · 2019: 23 · 2018: 20 · 2017: 21 · 2016: 17 · 2015: 10
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Matrix Biology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Bone and Dental Protein Studies
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Keywords
- matrikines, matrix metalloproteinases, elastin peptides, extracellular matrix degradation, MMP-1, MMP-2, MMP-8, MMP-9, MMP-12, neutrophil chemotaxis, cigarette smoke, leukotriene A4 hydrolase, corneal ulcer, atherosclerosis, tumor invasion, chronic obstructive pulmonary disease, inflammation
- MeSH terms
- Animals, Inflammation, Oligopeptides, Peptides, Extracellular Matrix Proteins, Matrix Metalloproteinases
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