Matrix metalloproteases in aberrant fibrotic tissue remodeling
Abstract
Pulmonary fibrosis, the final result of a large variety of interstitial lung diseases, is characterized by an aberrant remodeling of extracellular matrix (ECM) with a profound disturbance of the normal lung architecture. This remodeling includes the exaggerated accumulation of ECM components in the interstitial and alveolar spaces and the disruption of the basement membranes. It has long been accepted that matrix metalloproteases (MMPs) play an important role in the pathogenesis of pulmonary fibrosis, but the exact mechanisms are not well characterized. Several MMPs are strongly up-regulated in human and experimental lung fibrosis, highlighting the dynamic nature of scarring within the lung. MMPs are collectively capable of cleaving all components of the ECM and basement membranes, but importantly, they also process bioactive mediators such as growth factors, cytokines, chemokines, and cell-surface receptors. Moreover, they participate in the initiation of proteinase cascades that impact much broader substrates. Consequently, MMPs may play a central role in several interrelated processes observed in fibrosis such as ECM remodeling, basement-membrane breakdown, epithelial-cell apoptosis, cell migration, and angiogenesis.
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Myofibroblasts produce and release cytokines, extracellular matrix molecules such as collagens and fibronectin, and matrix metalloproteinases that regulate ECM turnover and remodeling.
“Myofibroblasts also synthesize and secrete cytokines, ECM molecules, such as COLLs and FN, and matrix metalloproteinases (MMPs) that control the ECM turnover and remodeling [22,23].”
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- Authors
- Pardo, A., & Selman, M.
- Affiliations
- Instituto Nacional de Enfermedades Respiratorias (MX)
- Corresponding author
- Pardo, Annie
- Venue
- Proceedings of the American Thoracic Society
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-06-01
- Volume
- 3
- Issue
- 4
- Pages
- 383-388
- ISSN
- 1546-3222 (ISSN-L)
- 1943-5665
- OpenAlex
- W2110499503
- Cited by
- 260
- References
- 62
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 14 · 2023: 6 · 2022: 14 · 2021: 14 · 2020: 10 · 2019: 13 · 2018: 14 · 2017: 18 · 2016: 13 · 2015: 21 · 2014: 13 · 2013: 15 · 2012: 12
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Proceedings of the American Thoracic Society (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Keywords
- matrix metalloproteinases, pulmonary fibrosis, interstitial lung disease, extracellular matrix remodeling, basement membrane degradation, epithelial apoptosis, cell migration, angiogenesis
- MeSH terms
- Animals, Extracellular Matrix, Humans, Metalloendopeptidases, Pulmonary Fibrosis
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