Temporal spatial expression and function of non-muscle myosin II isoforms IIA and IIB in scar remodeling
Open accessAbstract
Scar contracture is believed to be caused by the cell contractility during the remodeling phase of wound healing. Cell contractility is mediated by non-muscle myosin II (NMMII) and actin, but the temporal-spatial expression profile of NMMII isoforms A and B (IIA and IIB) during the remodeling phase and the role of NMMII in scar fibroblast tissue remodeling are unknown. Human scar tissue immunostained for IIA and IIB showed that both isoforms were highly expressed in scar tissue throughout the remodeling phase of repair and expression levels returned to normal after the remodeling phase. Human scar tissue immunostained for β-, γ- and α-smooth muscle actin showed that all isoforms were consistently expressed throughout the remodeling phase of repair. The β- and γ-smooth muscle actin were widely expressed throughout the dermis, but α-smooth muscle actin was only locally expressed within the dermis. In vitro, fibroblasts explanted from scar tissue were shown to express more IIA than fibroblasts explanted from normal tissue and scar fibroblasts contracted collagen lattices to a greater extent than normal fibroblasts. Blebbistatin was used to demonstrate the function of NMMII in collagen lattice contraction. In normal tissue, fibroblasts are stress-shielded from external tensile stress by the extracellular matrix. After dermal injury and during remodeling, fibroblasts are exposed to a matrix of increased stiffness. The effect of matrix stiffness on IIA and IIB expression was examined. IIA expression was greater in fibroblasts cultured in collagen lattices with increasing stiffness, and in fibroblasts cultured on glass slides compared with polyacrylamide gels with stiffness of 1 kPa. In conclusion, NMMII and actin isoform expression changes coordinately with the remodeling phase of repair, and NMMII is increased as matrix stiffness increases. As NMMII expression increases, so does the fibroblast contractility.
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Myofibroblasts are contractile; their stress fibers consist of alpha smooth muscle actin (αSMA) and non-muscle myosin type II and contract in actin-myosin fashion.
“Their microfilaments (also known as stress fibers) consist of alpha smooth muscle actin (αSMA) and non-muscle myosin type II (10) and can contract in typical actin-myosin fashion, albeit rather slowly compared to muscle actin myosin filaments.”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [10]
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Unraveling SSc Pathophysiology; The Myofibroblast
van Caam, A., Vonk, M., van den Hoogen, F., van Lent, P., & van der Kraan, P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02452 · Cited by 153 · see citing works
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Self-citation
- Authors
- Bond, J. E., Ho, T. Q., Selim, M. A., Hunter, C. L., Bowers, E. V., & Levinson, H.
- Affiliations
- Duke University (US)
- Duke Medical Center (US)
- Corresponding author
- Levinson, Howard
- Venue
- Laboratory Investigation
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 91
- Issue
- 4
- Pages
- 499-508
- ISSN
- 0023-6837 (ISSN-L)
- PMC
- PMC3407540
- OpenAlex
- W2071410302
- Cited by
- 46
- References
- 56
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 5 · 2014: 7 · 2013: 2 · 2012: 1
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Laboratory Investigation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (K08GM085562, GM085562-01)
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Keywords
- non-muscle myosin II, scar contracture, fibroblast contractility, collagen lattice contraction, extracellular matrix stiffness, smooth muscle actin, blebbistatin, scar fibroblasts
- MeSH terms
- Actins, Cicatrix, Elasticity, Extracellular Matrix, Female, Fibroblasts, Humans, Male, Middle Aged, Time Factors, Tissue Distribution, Wound Healing, Up-Regulation, Protein Isoforms, Dermis, Nonmuscle Myosin Type IIB, Nonmuscle Myosin Type IIA
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