β-Catenin–regulated myeloid cell adhesion and migration determine wound healing
Saeid Amini-Nik, … , Boris Hinz, Benjamin A. Alman
Saeid Amini-Nik, … , Boris Hinz, Benjamin A. Alman
Published May 16, 2014
Citation Information: J Clin Invest. 2014;124(6):2599-2610. https://doi.org/10.1172/JCI62059.
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β-Catenin–regulated myeloid cell adhesion and migration determine wound healing

Abstract

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.

Authors

Saeid Amini-Nik, Elizabeth Cambridge, Winston Yu, Anne Guo, Heather Whetstone, Puviindran Nadesan, Raymond Poon, Boris Hinz, Benjamin A. Alman

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Figure 7

Macrophages lacking β-catenin induce less TGF-β1 signaling, and TGF-β1 partially rescues the wound phenotype of mice lacking β-catenin in macrophages.

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Macrophages lacking β-catenin induce less TGF-β1 signaling, and TGF-β1 p...
(A) Quantitative RT-PCR analysis showing decreased TGF-β1 expression in β-catenin–deficient macrophages from Lysz-Cre Catnbtm2KEM ROSA-EYFP mice compared with that seen in their control littermates. (B) pSmad2 staining of fibroblasts that were exposed to either control (top panels) or β-catenin–deficient macrophages (bottom panels), indicating less pSmad2-positive cells in fibroblasts that were exposed to macrophages lacking β-catenin (quantified in C). Arrow shows pSmad2-positive cells. Scale bars: 100 μm. (D) Ki67 staining of fibroblasts that were exposed to either control macrophages (top panels) or to β-catenin–deficient macrophages (lower panels), indicating less Ki67-positive cells in fibroblasts that were exposed to macrophages lacking β-catenin (quantified in E). Arrow shows Ki67-positive cells. Scale bars: 200 μm. (F) Cell density quantification shows a significant increase in the number of cells in healing wounds in mice treated with TGF-β1 compared with those treated with vehicle. (G and H) Representative histology of a wound from a mouse treated with vehicle or TGF-β1 whose macrophages lacked β-catenin. Image in G is magnified in the lower panel; scale bars: 800 μm; 100 μm. Image in H is magnified in the lower panel; scale bars: 800 μm; 100 μm. Data represent the mean ± 95% CI of 7 mice.