Post-transcriptional regulation of alpha-smooth muscle actin determines the contractile phenotype of Dupuytren's nodular cells

Verjee, L.S., Midwood, K., Davidson, D., Eastwood, M. and Nanchahal, J. 2010. Post-transcriptional regulation of alpha-smooth muscle actin determines the contractile phenotype of Dupuytren's nodular cells. Journal of Cellular Physiology. 224 (3), pp. 681-690. https://doi.org/10.1002/jcp.22167

TitlePost-transcriptional regulation of alpha-smooth muscle actin determines the contractile phenotype of Dupuytren's nodular cells
AuthorsVerjee, L.S., Midwood, K., Davidson, D., Eastwood, M. and Nanchahal, J.
Abstract

The objective was to study Dupuytren's myofibroblast cells in constrained collagen matrices in order to more closely emulate their in vivo environment and, to correlate their contractility with -smooth muscle actin (-SMA) expression and determine if dermal fibroblasts regulate Dupuytren's myofibroblast phenotype. Isotonic and isometric force contraction by cells isolated from Dupuytren's nodules, palmar and non-palmar skin fibroblasts was measured in collagen matrices. The effect of co-culturing nodule cells with dermal fibroblasts on isometric contraction was examined. Isometric contraction was correlated with levels of -SMA mRNA by pcr and protein by Western blotting, and -SMA distribution assessed by immunofluorescence. Dupuytren's nodule cells exhibited similar levels of isotonic contraction to both palmar and non-palmar dermal fibroblasts. However, nodule cells generated high levels of isometric force (mean: 3.5 dynes/h), which continued to increase over 24 h to a maximum of 173 dynes. In contrast, dermal fibroblasts initially exhibited low levels of contraction (mean: 0.5 dynes/h) and reached tensional homeostasis on average after 15 h (range: 4–20 h), with a maximum force of 52 dynes. Although all three cell types had similar -SMA mRNA levels, increased levels of -SMA protein were observed in nodule cells compared to dermal fibroblasts. -SMA localised to stress fibres in 35% (range: 26–50%) of nodule cells compared to only 3% (range:0–6%) of dermal fibroblasts. Co-cultures of Dupuytren's cells and dermal fibroblasts showed no contractile differences. The contractile phenotype of Dupuytren's myofibroblasts is determined by increased -SMA protein distributed in stress fibres, not by cellular mRNA levels. Dupuytren's cell contractility is not influenced by dermal fibroblasts.

JournalJournal of Cellular Physiology
Journal citation224 (3), pp. 681-690
ISSN0021-9541
YearSep 2010
PublisherWiley
Digital Object Identifier (DOI)https://doi.org/10.1002/jcp.22167
Publication dates
PublishedSep 2010

Related outputs

Periostin modulates myofibroblast differentiation during full-thickness cutaneous wound repair
Elliott, C.G., Wang, J., Guo, X., Xu, S.W., Eastwood, M., Guan, J., Leask, A., Conway, S.J., Hamilton, D.W. and Shi-Wen, X. 2012. Periostin modulates myofibroblast differentiation during full-thickness cutaneous wound repair. Journal of Cell Science. 125 (1), pp. 121-132. https://doi.org/10.1242/jcs.087841

In vitro mesenchymal stem cell differentiation after mechanical stimulation
Sarraf, C., Otto, W.R. and Eastwood, M. 2011. In vitro mesenchymal stem cell differentiation after mechanical stimulation. Cell Proliferation. 44 (1), pp. 99-108. https://doi.org/10.1111/j.1365-2184.2010.00740.x

Thrombospondin 1 is a key mediator of transforming growth factor β-mediated cell contractility in systemic sclerosis via a mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)-dependent mechanism
Chen, Y., Leask, A., Abraham, D.J., Kennedy, L., Shi-Wen, X., Denton, C.P., Black, C.M., Verjee, L.S. and Eastwood, M. 2011. Thrombospondin 1 is a key mediator of transforming growth factor β-mediated cell contractility in systemic sclerosis via a mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)-dependent mechanism. Fibrogenesis and tissue repair. 4 (9). https://doi.org/10.1186/1755-1536-4-9

Expression of integrin β1 by fibroblasts is required for tissue repair in vivo
Liu, S., Shi-Wen, X., Blumbach, K., Eastwood, M., Denton, C.P., Eckes, B., Krieg, T., Abraham, D.J. and Leask, A. 2010. Expression of integrin β1 by fibroblasts is required for tissue repair in vivo. Journal of Cell Science. 123 (21), pp. 3674-3682. https://doi.org/10.1242/jcs.070672

Rosiglitazone alleviates the persistent fibrotic phenotype of lesional skin scleroderma fibroblasts
Shi-Wen, X., Eastwood, M., Stratton, R.J., Denton, C.P., Leask, A. and Abraham, D.J. 2010. Rosiglitazone alleviates the persistent fibrotic phenotype of lesional skin scleroderma fibroblasts. Rheumatology. 49 (2), pp. 259-263. https://doi.org/10.1093/rheumatology/kep371

Rac inhibition reverses the phenotype of fibrotic fibroblasts
Shi-Wen, X., Liu, S., Eastwood, M., Sonnylal, S., Denton, C.P., Abraham, D.J. and Leask, A. 2009. Rac inhibition reverses the phenotype of fibrotic fibroblasts. PLoS ONE. 4 (10) e7438. https://doi.org/10.1371/journal.pone.0007438

Requirement of transforming growth factor β–activated kinase 1 for transforming growth factor β–induced -smooth muscle actin expression and extracellular matrix contraction in fibroblasts
Shi-Wen, X., Parapuram, S.K., Pala, D., Chen, Y., Carter, D.E., Eastwood, M., Denton, C.P., Abraham, D.J. and Leask, A. 2009. Requirement of transforming growth factor β–activated kinase 1 for transforming growth factor β–induced -smooth muscle actin expression and extracellular matrix contraction in fibroblasts. Arthritis & Rheumatism. 60 (1), pp. 234-241. https://doi.org/10.1002/art.24223

Inducible lineage-specific deletion of TβRII in fibroblasts defines a pivotal regulatory role during adult skin wound healing
Denton, C.P., Khan, K., Hoyles, R.K., Shiwen, X., Leoni, P., Chen, Y., Eastwood, M. and Abraham, D.J. 2009. Inducible lineage-specific deletion of TβRII in fibroblasts defines a pivotal regulatory role during adult skin wound healing. Journal of Investigative Dermatology. 129 (1), pp. 194-204. https://doi.org/10.1038/jid.2008.171

Heparan sulfate-dependent ERK activation contributes to the overexpression of fibrotic proteins and enhanced contraction by scleroderma fibroblasts
Chen, Y., Leask, A., Abraham, D.J., Pala, D., Shiwen, X., Khan, K., Liu, S., Carter, D.E., Wilcox-Adelman, S., Goetinck, P.F., Denton, C.P., Black, C.M., Pitsillides, A.A., Sarraf, C. and Eastwood, M. 2008. Heparan sulfate-dependent ERK activation contributes to the overexpression of fibrotic proteins and enhanced contraction by scleroderma fibroblasts. Arthritis & Rheumatism. 58 (2), pp. 577-585. https://doi.org/10.1002/art.23146

Dynamic protrusive cell behaviour generates force and drives early matrix contraction by fibroblasts
Dahlmann-Noor, A.H., Martin-Martin, B., Eastwood, M., Khaw, P.T. and Bailly, M. 2007. Dynamic protrusive cell behaviour generates force and drives early matrix contraction by fibroblasts. Experimental Cell Research. 313 (20), pp. 4158-4169. https://doi.org/10.1016/j.yexcr.2007.07.040

Force generation of different human cardiac valve interstitial cells: relevance to individual valve function and tissue engineering
Smith, S., Taylor, P.M., Chester, A.H., Allen, S.P., Dreger, S.A., Eastwood, M. and Yacoub, M.H. 2007. Force generation of different human cardiac valve interstitial cells: relevance to individual valve function and tissue engineering. Journal of Heart Valve Disease. 16 (4), pp. 440-446.

FAK Is Required for TGFβ-induced JNK Phosphorylation in Fibroblasts: Implications for Acquisition of a Matrix-remodeling Phenotype
Shangxi, L., Shi-Wen, X., Kennedy, L., Pala, D., Chen, Y., Eastwood, M., Carter, D.E., Black, C.M., Abraham, D.J. and Leask, A. 2007. FAK Is Required for TGFβ-induced JNK Phosphorylation in Fibroblasts: Implications for Acquisition of a Matrix-remodeling Phenotype. Molecular Biology of the Cell. 18 (6), pp. 2169-2178. https://doi.org/10.1091/mbc.E06-12-1121

CCN2 is necessary for the function of mouse embryonic fibroblasts
Kennedy, L., Liu, S., Shi-Wen, X., Chen, Y., Eastwood, M., Carter, D.E., Lyon, K.M., Black, C.M., Abraham, D.J. and Leask, A. 2007. CCN2 is necessary for the function of mouse embryonic fibroblasts. Experimental Cell Research. 313 (5), pp. 952-964. https://doi.org/10.1016/j.yexcr.2006.12.006

Contribution of activin receptor-like kinase 5 (transforming growth factor beta receptor type I) signaling to the fibrotic phenotype of scleroderma fibroblasts
Chen, Y., Shi-Wen, X., Eastwood, M., Black, C.M., Denton, C.P., Leask, A. and Abraham, D.J. 2006. Contribution of activin receptor-like kinase 5 (transforming growth factor beta receptor type I) signaling to the fibrotic phenotype of scleroderma fibroblasts. Arthritis & Rheumatism. 54 (4), pp. 1309-1316. https://doi.org/10.1002/art.21725

Matrix contraction by dermal fibroblasts requires transforming growth Factor-ß /activin-linked kinase 5, heparan sulfate-containing proteoglycans, and MEK/ERK: insights into pathological scarring in chronic fibrotic disease
Chen, Y., Shi-Wen, X., van Beek, J., Kennedy, L., McLeod, M., Renzoni, E.A., Bou-Gharios, G., Wilcox-Adelman, S., Goetinck, P.F., Eastwood, M., Black, C.M., Abraham, D.J. and Leask, A. 2005. Matrix contraction by dermal fibroblasts requires transforming growth Factor-ß /activin-linked kinase 5, heparan sulfate-containing proteoglycans, and MEK/ERK: insights into pathological scarring in chronic fibrotic disease. American Journal of Pathology. 167 (6), pp. 1699-1711.

Cell proliferation rates in an artificial tissue-engineered environment
Sarraf, C., Harris, A.B., McCulloch, A.D. and Eastwood, M. 2005. Cell proliferation rates in an artificial tissue-engineered environment. Cell Proliferation. 38 (4), pp. 215-221. https://doi.org/10.1111/j.1365-2184.2005.00347.x

Activation of Key Profibrotic Mechanisms in Transgenic Fibroblasts Expressing Kinase-deficient Type II Transforming Growth Factor beta-receptor (T beta RII delta k)
Denton, C.P., Lindahl, G.E., Khan, K., Shiwen, X., Ong, V.H., Gaspar, N.J., Lazaridis, K., Edwards, D.R., Leask, A., Eastwood, M., Leoni, P., Renzoni, E.A., Bou-Gharios, G., Abraham, D.J. and Black, C.M. 2005. Activation of Key Profibrotic Mechanisms in Transgenic Fibroblasts Expressing Kinase-deficient Type II Transforming Growth Factor beta-receptor (T beta RII delta k). Journal of Biological Chemistry. 280 (16), pp. 16053-16065. https://doi.org/10.1074/jbc.M413134200

Stem cells, tissue engineering and the mechanical environment
Sarraf, C. and Eastwood, M. 2005. Stem cells, tissue engineering and the mechanical environment. in: Ashammakhi, N.A. and Reis, R.L. (ed.) Topics in tissue engineering Biomaterials and tissue engineering group.

Endothelin-1 promotes myofibroblast induction through the ETA receptor via a rac/phosphoinositide 3-kinase/akt-dependent pathway and is essential for the enhanced contractile phenotype of fibrotic fibroblasts
Shi-Wen, X., Chen, Y., Denton, C.P., Eastwood, M., Renzoni, E.A., Bou-Gharios, G., Pearson, J., Dashwood, M., du Bois, R., Black, C.M., Leask, A. and Abraham, D.J. 2004. Endothelin-1 promotes myofibroblast induction through the ETA receptor via a rac/phosphoinositide 3-kinase/akt-dependent pathway and is essential for the enhanced contractile phenotype of fibrotic fibroblasts. Molecular Biology of the Cell. 15 (6), pp. 2707-2719. https://doi.org/10.1091/mbc.E03-12-0902

New multi-cue bioreactor for tissue engineering of tubular cardiovascular samples under physiological conditions
McCulloch, A.D., Harris, A.B., Sarraf, C. and Eastwood, M. 2004. New multi-cue bioreactor for tissue engineering of tubular cardiovascular samples under physiological conditions. Tissue Engineering. 10 (3/4), pp. 565-573.

Heart valve and arterial tissue engineering
Sarraf, C., Harris, A.B., McCulloch, A.D. and Eastwood, M. 2003. Heart valve and arterial tissue engineering. Cell Proliferation. 36 (5), pp. 241-254. https://doi.org/10.1046/j.1365-2184.2003.00281.x

Evidence for sequential utilization of fibronectin, vitronectin, and collagen during fibroblast-mediated collagen contraction
Sethi, K.K., Yannas, I.V., Mudera, V., Eastwood, M., McFarland, C. and Brown, R.A. 2002. Evidence for sequential utilization of fibronectin, vitronectin, and collagen during fibroblast-mediated collagen contraction. Wound Repair and Regeneration. 10 (6), pp. 397 -408. https://doi.org/10.1046/j.1524-475X.2002.10609.x

Enhanced fibroblast contraction of 3D collagen lattices and integrin expression by TGF-β1 and -β: mechanoregulatory growth factors?
Brown, R.A., Sethi, K.K., Gwanmesia, I., Raemdonck, D., Eastwood, M. and Mudera, V. 2002. Enhanced fibroblast contraction of 3D collagen lattices and integrin expression by TGF-β1 and -β: mechanoregulatory growth factors? Experimental Cell Research. 274 (2), pp. 310-322. https://doi.org/10.1006/excr.2002.5471

Tissue engineering of biological cardiovascular system surrogates
Sarraf, C., Harris, A.B., McCulloch, A.D. and Eastwood, M. 2002. Tissue engineering of biological cardiovascular system surrogates. Heart, Lung & Circulation. 11 (3), pp. 142-150. https://doi.org/10.1046/j.1444-2892.2002.00150.x

Identification of a novel stretch-responsive skeletal muscle gene (smpx)
Kemp, T.J., Sadusky, T.J., Simon, M., Brown, R.A., Eastwood, M., Sassoon, D.A. and Coulton, G.R. 2001. Identification of a novel stretch-responsive skeletal muscle gene (smpx). Genomics. 72 (3), pp. 260-271. https://doi.org/10.1006/geno.2000.6461

Permalink - https://westminsterresearch.westminster.ac.uk/item/901z7/post-transcriptional-regulation-of-alpha-smooth-muscle-actin-determines-the-contractile-phenotype-of-dupuytren-s-nodular-cells


Share this

Usage statistics

136 total views
0 total downloads
These values cover views and downloads from WestminsterResearch and are for the period from September 2nd 2018, when this repository was created.