Limits...
Beta-catenin and transforming growth factor beta have distinct roles regulating fibroblast cell motility and the induction of collagen lattice contraction.

Poon R, Nik SA, Ahn J, Slade L, Alman BA - BMC Cell Biol. (2009)

Bottom Line: Treating wild-type cells or primary human fibroblasts with dickkopf-1, which inhibits beta-catenin, or lithium, which stimulates beta-catenin produced similar results.Scratch wound assays and Boyden chamber motility studies using these same cells found that beta-catenin positively regulated cell motility, while transforming growth factor beta had little effect.Cell motility and the induction of collagen lattice contraction are not always coupled, and are likely regulated by different intracellular mechanisms.

View Article: PubMed Central - HTML - PubMed

Affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. Raymond.poon@sickkids.ca

ABSTRACT

Background: beta-catenin and transforming growth factor beta signaling are activated in fibroblasts during wound healing. Both signaling pathways positively regulate fibroblast proliferation during this reparative process, and the effect of transforming growth factor beta is partially mediated by beta-catenin. Other cellular processes, such as cell motility and the induction of extracellular matrix contraction, also play important roles during wound repair. We examined the function of beta-catenin and its interaction with transforming growth factor beta in cell motility and the induction of collagen lattice contraction.

Results: Floating three dimensional collagen lattices seeded with cells expressing conditional and stabilized beta-catenin alleles, showed a modest negative relationship between beta-catenin level and the degree of lattice contraction. Transforming growth factor beta had a more dramatic effect, positively regulating lattice contraction. In contrast to the situation in the regulation of cell proliferation, this effect of transforming growth factor beta was not mediated by beta-catenin. Treating wild-type cells or primary human fibroblasts with dickkopf-1, which inhibits beta-catenin, or lithium, which stimulates beta-catenin produced similar results. Scratch wound assays and Boyden chamber motility studies using these same cells found that beta-catenin positively regulated cell motility, while transforming growth factor beta had little effect.

Conclusion: This data demonstrates the complexity of the interaction of various signaling pathways in the regulation of cell behavior during wound repair. Cell motility and the induction of collagen lattice contraction are not always coupled, and are likely regulated by different intracellular mechanisms. There is unlikely to be a single signaling pathway that acts as master regulator of fibroblast behavior in wound repair. beta-catenin plays dominant role regulating cell motility, while transforming growth factor beta plays a dominant role regulating the induction of collagen lattice contraction.

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β-catenin stabilization has a minor effect on collagen lattice contraction compared to transforming growth factor β. A. Means and 95% confidence intervals for collagen lattice areas as observed over seven days for fibroblasts from mice expressing stabilized β-catenin alleles or wild type littermates treated with the adenovirus expressing cre recombinase, also treated with either transforming growth factor β, or carrier. There is a statistically significant difference between transforming growth factor β and carrier treatment for all time points after day three, and a statistically significant difference between fibroblasts in which the stabilized β-catenin allele was activated compared to fibroblasts from wild type mice for the time points with an asterisk above the data points. Data obtained using serum free media is shown. B. Representative photographs of the collagen lattices at day seven.
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Figure 3: β-catenin stabilization has a minor effect on collagen lattice contraction compared to transforming growth factor β. A. Means and 95% confidence intervals for collagen lattice areas as observed over seven days for fibroblasts from mice expressing stabilized β-catenin alleles or wild type littermates treated with the adenovirus expressing cre recombinase, also treated with either transforming growth factor β, or carrier. There is a statistically significant difference between transforming growth factor β and carrier treatment for all time points after day three, and a statistically significant difference between fibroblasts in which the stabilized β-catenin allele was activated compared to fibroblasts from wild type mice for the time points with an asterisk above the data points. Data obtained using serum free media is shown. B. Representative photographs of the collagen lattices at day seven.

Mentions: Transforming growth factor β one is known to induce contraction of three dimensional collagen lattices seeded with fibroblasts [11]. Since β-catenin partially mediates transforming growth factor β regulated fibroblast cell proliferation[16], we examined if transforming growth factor β induced collagen lattice contraction might be mediated by β-catenin. Contraction rate was compared between wild type and β-catenin cells treated with transforming growth factor β. The effect of transforming growth factor β induced lattice contraction was not dependent β-catenin (Fig. 2). The relationship of β-catenin stabilization and transforming growth factor β treatment was examined in cells expressing stabilized β-catenin alleles. There was a small effect of β-catenin stabilization compared to transforming growth factor β treatment (Fig. 3). In contrast to its role in fibroblast proliferation, transforming growth factor β induces contraction of collagen lattices independent of β-catenin.


Beta-catenin and transforming growth factor beta have distinct roles regulating fibroblast cell motility and the induction of collagen lattice contraction.

Poon R, Nik SA, Ahn J, Slade L, Alman BA - BMC Cell Biol. (2009)

β-catenin stabilization has a minor effect on collagen lattice contraction compared to transforming growth factor β. A. Means and 95% confidence intervals for collagen lattice areas as observed over seven days for fibroblasts from mice expressing stabilized β-catenin alleles or wild type littermates treated with the adenovirus expressing cre recombinase, also treated with either transforming growth factor β, or carrier. There is a statistically significant difference between transforming growth factor β and carrier treatment for all time points after day three, and a statistically significant difference between fibroblasts in which the stabilized β-catenin allele was activated compared to fibroblasts from wild type mice for the time points with an asterisk above the data points. Data obtained using serum free media is shown. B. Representative photographs of the collagen lattices at day seven.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2691404&req=5

Figure 3: β-catenin stabilization has a minor effect on collagen lattice contraction compared to transforming growth factor β. A. Means and 95% confidence intervals for collagen lattice areas as observed over seven days for fibroblasts from mice expressing stabilized β-catenin alleles or wild type littermates treated with the adenovirus expressing cre recombinase, also treated with either transforming growth factor β, or carrier. There is a statistically significant difference between transforming growth factor β and carrier treatment for all time points after day three, and a statistically significant difference between fibroblasts in which the stabilized β-catenin allele was activated compared to fibroblasts from wild type mice for the time points with an asterisk above the data points. Data obtained using serum free media is shown. B. Representative photographs of the collagen lattices at day seven.
Mentions: Transforming growth factor β one is known to induce contraction of three dimensional collagen lattices seeded with fibroblasts [11]. Since β-catenin partially mediates transforming growth factor β regulated fibroblast cell proliferation[16], we examined if transforming growth factor β induced collagen lattice contraction might be mediated by β-catenin. Contraction rate was compared between wild type and β-catenin cells treated with transforming growth factor β. The effect of transforming growth factor β induced lattice contraction was not dependent β-catenin (Fig. 2). The relationship of β-catenin stabilization and transforming growth factor β treatment was examined in cells expressing stabilized β-catenin alleles. There was a small effect of β-catenin stabilization compared to transforming growth factor β treatment (Fig. 3). In contrast to its role in fibroblast proliferation, transforming growth factor β induces contraction of collagen lattices independent of β-catenin.

Bottom Line: Treating wild-type cells or primary human fibroblasts with dickkopf-1, which inhibits beta-catenin, or lithium, which stimulates beta-catenin produced similar results.Scratch wound assays and Boyden chamber motility studies using these same cells found that beta-catenin positively regulated cell motility, while transforming growth factor beta had little effect.Cell motility and the induction of collagen lattice contraction are not always coupled, and are likely regulated by different intracellular mechanisms.

View Article: PubMed Central - HTML - PubMed

Affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. Raymond.poon@sickkids.ca

ABSTRACT

Background: beta-catenin and transforming growth factor beta signaling are activated in fibroblasts during wound healing. Both signaling pathways positively regulate fibroblast proliferation during this reparative process, and the effect of transforming growth factor beta is partially mediated by beta-catenin. Other cellular processes, such as cell motility and the induction of extracellular matrix contraction, also play important roles during wound repair. We examined the function of beta-catenin and its interaction with transforming growth factor beta in cell motility and the induction of collagen lattice contraction.

Results: Floating three dimensional collagen lattices seeded with cells expressing conditional and stabilized beta-catenin alleles, showed a modest negative relationship between beta-catenin level and the degree of lattice contraction. Transforming growth factor beta had a more dramatic effect, positively regulating lattice contraction. In contrast to the situation in the regulation of cell proliferation, this effect of transforming growth factor beta was not mediated by beta-catenin. Treating wild-type cells or primary human fibroblasts with dickkopf-1, which inhibits beta-catenin, or lithium, which stimulates beta-catenin produced similar results. Scratch wound assays and Boyden chamber motility studies using these same cells found that beta-catenin positively regulated cell motility, while transforming growth factor beta had little effect.

Conclusion: This data demonstrates the complexity of the interaction of various signaling pathways in the regulation of cell behavior during wound repair. Cell motility and the induction of collagen lattice contraction are not always coupled, and are likely regulated by different intracellular mechanisms. There is unlikely to be a single signaling pathway that acts as master regulator of fibroblast behavior in wound repair. beta-catenin plays dominant role regulating cell motility, while transforming growth factor beta plays a dominant role regulating the induction of collagen lattice contraction.

Show MeSH
Related in: MedlinePlus