Deep Tissue Injury in Development of Pressure Ulcers: A Decrease of Inflammasome Activation and Changes in Human Skin Morphology in Response to Aging and Mechanical Load
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Molecular mechanisms leading to pressure ulcer development are scarce in spite of high mortality of patients. Development of pressure ulcers that is initially observed as deep tissue injury is multifactorial. We postulate that biomechanical forces and inflammasome activation, together with ischemia and aging, may play a role in pressure ulcer development. To test this we used a newly-developed bio-mechanical model in which ischemic young and aged human skin was subjected to a constant physiological compressive stress (load) of 300 kPa (determined by pressure plate analyses of a person in a reclining position) for 0.5-4 hours. Collagen orientation was assessed using polarized light, whereas inflammasome proteins were quantified by immunoblotting. Loaded skin showed marked changes in morphology and NLRP3 inflammasome protein expression. Sub-epidermal separations and altered orientation of collagen fibers were observed in aged skin at earlier time points. Aged skin showed significant decreases in the levels of NLRP3 inflammasome proteins. Loading did not alter NLRP3 inflammasome proteins expression in aged skin, whereas it significantly increased their levels in young skin. We conclude that aging contributes to rapid morphological changes and decrease in inflammasome proteins in response to tissue damage, suggesting that a decline in the innate inflammatory response in elderly skin could contribute to pressure ulcer pathogenesis. Observed morphological changes suggest that tissue damage upon loading may not be entirely preventable. Furthermore, newly developed model described here may be very useful in understanding the mechanisms of deep tissue injury that may lead towards development of pressure ulcers.
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The inflammasome is implicated in the development of chronic wounds.
“Recent studies have implicated the inflammasome, a multiprotein complex of the innate immune system responsible for activation and release of IL-1β from several skin cell types, in the development of chronic wounds (31, 32).”
From Wound repair and regeneration: Mechanisms, signaling, and translation (2014) · cites this paper as [32]
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- Authors
- Stojadinovic, O., Minkiewicz, J., Sawaya, A., Bourne, J. W., Torzilli, P., de Rivero Vaccari, J. P., Dietrich, W. D., Keane, R. W., & Tomic-Canic, M.
- Affiliations
- University of Miami (US)
- Hospital for Special Surgery (US)
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-08-14
- Volume
- 8
- Issue
- 8
- Pages
- e69223
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3743891
- OpenAlex
- W2145997121
- Cited by
- 77
- References
- 76
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 7 · 2022: 4 · 2021: 14 · 2020: 9 · 2019: 8 · 2018: 3 · 2017: 7 · 2016: 7 · 2015: 7 · 2014: 5 · 2013: 1
- FWCI
- 20.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Hospital for Special Surgery
- National Institutes of Health (TL1TR000459, UL1TR000457)
- National Institute on Aging (AG030673, R21AG030673)
- National Institute of Diabetes and Digestive and Kidney Diseases (RC1DK086364, DK086364)
- National Institute of Neurological Disorders and Stroke (NS059836, R01NS059836)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21AR060562, AR060562)
- National Center for Research Resources (TL1RR024998)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Health Professions › Occupational Therapy › Pressure Ulcer Prevention and Management
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Keywords
- pressure ulcers, deep tissue injury, NLRP3 inflammasome, skin aging, mechanical loading, collagen fiber orientation, skin ischemia, biomechanical modeling, skin morphology
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Adult, Aging, Biomechanical Phenomena, Carrier Proteins, Collagen, Pressure Ulcer, Female, Humans, Male, Materials Testing, Middle Aged, Models, Biological, Pressure, Skin, Stress, Mechanical, Time Factors, Dermis, Interleukin-1beta, Inflammasomes
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