Constitutive phosphorylation of focal adhesion kinase is involved in the myofibroblast differentiation of scleroderma fibroblasts
Open accessAbstract
Most of the cultured scleroderma fibroblasts have been reported to be myofibroblasts that have the ability to express alpha smooth muscle actin (alphaSMA). It is reported that, in human lung fibroblasts, alphaSMA is induced by transforming growth factor-beta (TGF-beta), which requires focal adhesion kinase (FAK) phosphorylation on its Tyr-397 site. In this study, we investigated how alphaSMA expression is upregulated in cultured scleroderma fibroblasts. 4-amino-5-(4-chlorophenyl)-7-(butyl)pyrazolo[3,4-d]pyrimidine, which is a pharmacologic inhibitor of FAK/Src, markedly diminished upregulated alphaSMA expression in scleroderma fibroblasts as well as in normal fibroblasts stimulated with TGF-beta. Likewise, alphaSMA expression was significantly reduced in sclerderma fibroblasts transfected with kinase-deficient FAK mutant. FAK phosphorylation levels on Tyr-397 in scleroderma fibroblasts were significantly higher than those in normal fibroblasts. Both alphaSMA expression and FAK phosphorylation levels in scleroderma fibroblasts were markedly diminished by the treatment with TGF-beta antisense oligonucleotide. These results indicate that the constitutive phosphorylation of FAK, which is possibly because of the autocrine TGF-beta signaling, may play an important role in alphaSMA expression in scleroderma fibroblasts.
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Skin (myo)fibroblasts of SSc patients show more activation of focal adhesion kinase (FAK) in vitro than those of controls.
“For example, skin (myo) fibroblasts of SSc patients show more activation of focal adhesion kinase (FAK) in vitro than those of controls (97).”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [97]
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- Authors
- Mimura, Y., Ihn, H., Jinnin, M., Asano, Y., Yamane, K., & Tamaki, K.
- Affiliations
- The University of Tokyo (JP)
- Corresponding author
- Ihn, Hironobu
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2005-05
- Volume
- 124
- Issue
- 5
- Pages
- 886-892
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W1979973473
- Cited by
- 70
- References
- 53
- Citations by year
- 2025: 1 · 2024: 5 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 4 · 2017: 3 · 2015: 3 · 2014: 1 · 2013: 5 · 2012: 7
- FWCI
- 4.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Keywords
- focal adhesion kinase, constitutive phosphorylation, myofibroblast differentiation, alpha-smooth muscle actin, TGF-beta
- MeSH terms
- Actins, Cell Differentiation, Cells, Cultured, Fibroblasts, Humans, Oligopeptides, Phosphorylation, Protein-Tyrosine Kinases, Scleroderma, Systemic, Signal Transduction, Transforming Growth Factor beta, Oligonucleotides, Antisense, Focal Adhesion Protein-Tyrosine Kinases, Focal Adhesion Kinase 1
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