β-Catenin-regulated myeloid cell adhesion and migration determine wound healing.
A β-catenin/T cell factor-dependent transcriptional program is critical during cutaneous wound repair for the regulation of scar size; however, the relative contribution of β-catenin activity and function in specific cell types in the granulation tissue during the healing process is unknown. Here, cell lineage tracing revealed that cells in which β-catenin is transcriptionally active express a gene profile that is characteristic of the myeloid lineage. Mice harboring a macrophage-specific deletion of the gene encoding β-catenin exhibited insufficient skin wound healing due to macrophage-specific defects in migration, adhesion to fibroblasts, and ability to produce TGF-β1. In irradiated mice, only macrophages expressing β-catenin were able to rescue wound-healing deficiency. Evaluation of scar tissue collected from patients with hypertrophic and normal scars revealed a correlation between the number of macrophages within the wound, β-catenin levels, and cellularity. Our data indicate that β-catenin regulates myeloid cell motility and adhesion and that β-catenin-mediated macrophage motility contributes to the number of mesenchymal cells and ultimate scar size following cutaneous injury.
Saeid
S
Amini-Nik
Elizabeth
E
Cambridge
Winston
W
Yu
Anne
A
Guo
Heather
H
Whetstone
Puviindran
P
Nadesan
Raymond
R
Poon
Boris
B
Hinz
Benjamin A
BA
Alman
D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D019070:Cell Lineage / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology; D017439:Cicatrix, Hypertrophic / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000166:cytology / Q000502:physiology*; D012867:Skin / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D051820:TCF Transcription Factors / Q000235:genetics / Q000502:physiology; D059467:Transcriptome; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D051820:TCF Transcription Factors; D053773:Transforming Growth Factor beta1; D051176:beta Catenin