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


CONCLUSIONS
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.
Program in Developmental and Stem Cell Biology, Hospital for Sick Children, University of Toronto, Toronto, ON, Canada. Raymond.poon@sickkids.ca
Raymond
R
Poon
Saeid Amini
SA
Nik
Jessica
J
Ahn
Laura
L
Slade
Benjamin A
BA
Alman
D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology; D051379:Mice; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014945:Wound Healing; D051176:beta Catenin / Q000378:metabolism*
D000199:Actins; C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; D051176:beta Catenin; D003094:Collagen; D008094:Lithium