The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
TNF-α Suppresses α-Smooth Muscle Actin Expression in Human Dermal Fibroblasts: An Implication for Abnormal Wound Healing
Open accessAbstract
Abnormal wound healing encompasses a wide spectrum, from chronic wounds to hypertrophic scars. Both conditions are associated with an abnormal cytokine profile in the wound bed. In this study, we sought to understand the dynamic relationships between myofibroblast differentiation and mechanical performance of the collagen matrix under tissue growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) stimulation. We found TGF-beta increased alpha-smooth muscle actin (alpha-SMA) and TNF-alpha alone decreased the basal alpha-SMA expression. When TGF-beta1 and TNF-alpha were both added, the alpha-SMA expression was suppressed below the baseline. Real-time PCR showed that TNF-alpha suppresses TGF-beta1-induced myofibroblast (fibroproliferative) phenotypic genes, for example, alpha-SMA, collagen type 1A, and fibronectin at the mRNA level. TNF-alpha suppresses TGF-beta1-induced gene expression by affecting its mRNA stability. Our results further showed that TNF-alpha inhibits TGF-beta1-induced Smad-3 phosphorylation via Jun N-terminal kinase signaling. Mechanical testing showed that TNF-alpha decreases the stiffness and contraction of the lattices after 5 days in culture. We proposed that changes in alpha-SMA, collagen, and fibronectin expression result in decreased contraction and stiffness of collagen matrices. Therefore, the balance of cytokines in a wound defines the mechanical properties of the extracellular matrix and optimal wound healing.
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“However, in dermal fibroblasts TNFα can inhibit αSMA expression by inhibiting TGFβ signaling (124).”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [124]
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Myofibroblasts and mechano-regulation of connective tissue remodelling
Tomasek, J. J., Gabbiani, G., Hinz, B., Chaponnier, C., & Brown, R. A. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm809 · Cited by 4,290
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The myofibroblast in wound healing and fibrocontractive diseases
Gabbiani, G. (2003) · The Journal of Pathology · doi:10.1002/path.1427 · Cited by 1,630
Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity
Hinz, B., Celetta, G., Tomasek, J. J., Gabbiani, G., & Chaponnier, C. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.9.2730 · Cited by 1,288
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Cell and molecular mechanics of biological materials
Bao, G., & Suresh, S. (2003) · Nature Materials · doi:10.1038/nmat1001 · Cited by 1,063
Accelerated Healing of Incisional Wounds in Rats Induced by Transforming Growth Factor-β
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Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response
Ashcroft, G. S., Yang, X., Glick, A. B., Weinstein, M., Letterio, J. J., Mizel, D. E., Anzano, M., Greenwell-Wild, T., Wahl, S. M., Deng, C., et al. (1999) · Nature Cell Biology · doi:10.1038/12971 · Cited by 911
Analysis of the acute and chronic wound environments: the role of proteases and their inhibitors
Trengove, N. J., Stacey, M. C., Macauley, S., Bennett, N., Gibson, J., Burslem, F., Murphy, G., & Schultz, G. (1999) · Wound Repair and Regeneration · doi:10.1046/j.1524-475x.1999.00442.x · Cited by 908
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PERSPECTIVE ARTICLE: Growth factors and cytokines in wound healing
Barrientos, S., Stojadinovic, O., Golinko, M. S., Brem, H., & Tomic‐Canic, M. (2008) · Wound Repair and Regeneration · doi:10.1111/j.1524-475x.2008.00410.x · Cited by 3,583
Wound Healing: A Cellular Perspective
Rodrigues, M., Kosaric, N., Bonham, C. A., & Gurtner, G. C. (2018) · Physiological Reviews · doi:10.1152/physrev.00067.2017 · Cited by 3,211
Greaves, N. S., Ashcroft, K. J., Baguneid, M. S., & Bayat, A. (2013) · Journal of Dermatological Science · doi:10.1016/j.jdermsci.2013.07.008 · Cited by 493
Jung, M., Ma, Y., Iyer, R. P., DeLeon‐Pennell, K. Y., Yabluchanskiy, A., Garrett, M. R., & Lindsey, M. L. (2017) · Basic Research in Cardiology · doi:10.1007/s00395-017-0622-5 · Cited by 453
Kant, V., Gopal, A., Pathak, N. N., Kumar, P., Tandan, S. K., & Kumar, D. (2014) · International Immunopharmacology · doi:10.1016/j.intimp.2014.03.009 · Cited by 366
Metadata
- Authors
- Goldberg, M. T., Han, Y.-P., Yan, C., Shaw, M. C., & Garner, W. L.
- Affiliations
- University of Southern California (US)
- California Lutheran University (US)
- Corresponding author
- Garner, Warren L.
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 127
- Issue
- 11
- Pages
- 2645-2655
- ISSN
- 0022-202X (ISSN-L)
- PMC
- PMC2366884
- OpenAlex
- W2010619374
- Cited by
- 219
- References
- 42
- Citations by year
- 2026: 10 · 2025: 19 · 2024: 17 · 2023: 6 · 2022: 14 · 2021: 16 · 2020: 12 · 2019: 12 · 2018: 12 · 2017: 14 · 2016: 7 · 2015: 15 · 2014: 13 · 2013: 5 · 2012: 13
- FWCI
- 7.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R01GM050967)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR051558)
- Topics
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
- Keywords
- TNF-α, alpha-smooth muscle actin, TGF-β1, dermal fibroblasts, myofibroblast differentiation, wound healing, hypertrophic scars, chronic wounds, fibronectin, mRNA stability, JNK signaling, extracellular matrix stiffness, collagen matrix contraction, cytokine balance
- MeSH terms
- Actins, Cells, Cultured, Chronic Disease, Fibroblasts, Fibronectins, Humans, RNA, Messenger, Tumor Necrosis Factor-alpha, Wound Healing, Wounds and Injuries, Signal Transduction, Cicatrix, Hypertrophic, Dermis, Mitogen-Activated Protein Kinase Kinases, Collagen Type I, Smad3 Protein, Transforming Growth Factor beta1
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