Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity
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To evaluate whether α-smooth muscle actin (α-SMA) plays a role in fibroblast contractility, we first compared the contractile activity of rat subcutaneous fibroblasts (SCFs), expressing low levels of α-SMA, with that of lung fibroblasts (LFs), expressing high levels of α-SMA, with the use of silicone substrates of different stiffness degrees. On medium stiffness substrates the percentage of cells producing wrinkles was similar to that of α-SMA–positive cells in each fibroblast population. On high stiffness substrates, wrinkle production was limited to a subpopulation of LFs very positive for α-SMA. In a second approach, we measured the isotonic contraction of SCF- and LF-populated attached collagen lattices. SCFs exhibited 41% diameter reduction compared with 63% by LFs. TGFβ1 increased α-SMA expression and lattice contraction by SCFs to the levels of LFs; TGFβ-antagonizing agents reduced α-SMA expression and lattice contraction by LFs to the level of SCFs. Finally, 3T3 fibroblasts transiently or permanently transfected with α-SMA cDNA exhibited a significantly higher lattice contraction compared with wild-type 3T3 fibroblasts or to fibroblasts transfected with α-cardiac and β- or γ-cytoplasmic actin. This took place in the absence of any change in smooth muscle or nonmuscle myosin heavy-chain expression. Our results indicate that an increased α-SMA expression is sufficient to enhance fibroblast contractile activity.
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The αSMA-high, matrix-producing-high state is reversible, supported by the responsiveness of matrix production and the αSMA promoter to extracellular cues including substrate stiffness.
“the responsiveness of matrix production by fibroblasts and the αSMA promoter to a range of extracellular cues, including substrate stiffness, supports the idea that the αSMA-high, matrix producing-high state is reversible63,64,137–139.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [137]
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- Authors
- Hinz, B., Celetta, G., Tomasek, J. J., Gabbiani, G., & Chaponnier, C.
- Affiliations
- University of Geneva (CH)
- Venue
- Molecular Biology of the Cell
- Published
- 2001-09
- Volume
- 12
- Issue
- 9
- Pages
- 2730-2741
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC59708
- OpenAlex
- W2160698607
- Cited by
- 1,288
- References
- 3
- Citations by year
- 2026: 46 · 2025: 53 · 2024: 72 · 2023: 68 · 2022: 80 · 2021: 96 · 2020: 77 · 2019: 79 · 2018: 82 · 2017: 65 · 2016: 56 · 2015: 63 · 2014: 58 · 2013: 55 · 2012: 44
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Keywords
- alpha-smooth muscle actin, fibroblast contractility, lung fibroblasts, substrate stiffness, collagen lattice contraction, TGF-β1, TGF-beta antagonists, 3T3 fibroblasts, actin isoforms, myosin heavy chain
- MeSH terms
- Actins, Animals, Cells, Cultured, Collagen, Fibroblasts, Gels, Microscopy, Fluorescence, Muscle, Smooth, Silicon, Transfection, Blotting, Western, Up-Regulation, Transforming Growth Factor beta, 3T3 Cells, Protein Isoforms, Cell Size, Mice, Rats
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