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?-Catenin-regulated myeloid cell adhesion and migration determine wound healing.

ABSTRACT: A ?-catenin/T cell factor-dependent transcriptional program is critical during cutaneous wound repair for the regulation of scar size; however, the relative contribution of ?-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 ?-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 ?-catenin exhibited insufficient skin wound healing due to macrophage-specific defects in migration, adhesion to fibroblasts, and ability to produce TGF-?1. In irradiated mice, only macrophages expressing ?-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, ?-catenin levels, and cellularity. Our data indicate that ?-catenin regulates myeloid cell motility and adhesion and that ?-catenin-mediated macrophage motility contributes to the number of mesenchymal cells and ultimate scar size following cutaneous injury.

SUBMITTER: Amini-Nik S

PROVIDER: S-EPMC4089463 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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β-Catenin-regulated myeloid cell adhesion and migration determine wound healing.

Amini-Nik Saeid S Cambridge Elizabeth E Yu Winston W Guo Anne A Whetstone Heather H Nadesan Puviindran P Poon Raymond R Hinz Boris B Alman Benjamin A BA

The Journal of clinical investigation 20140516 6

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 deleti ...[more]

PMID: 24837430

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Project description:In addition to its analgesic functions, the peripheral opioid receptor system affects skin homeostasis by influencing cell differentiation, migration and adhesion; also, wound healing is altered in ?-opioid receptor knockout mice (DOPr(-/-) ). Hence, we investigated ?-opioid receptor effects on the expression of several proteins of the desmosomal junction complex and on the migratory behaviour of keratinocytes.Expression levels of desmosomal cadherins in wild-type and DOPr(-/-) mice, and the morphology of intercellular adhesion in human keratinocytes were analysed by immunofluorescence. To investigate the ?-opioid receptor activation pathway, protein expression was studied using Western blot and its effect on cellular migration determined by in vitro live cell migration recordings from human keratinocytes.Expression of the desmosomal cadherins, desmogleins 1 and 4, was up-regulated in skin from DOPr(-/-) mice, and down-regulated in ?-opioid receptor-overexpressing human keratinocytes. The localization of desmoplakin expression was rearranged from linear arrays emanating from cell borders to puncta in cell periphery, resulting in less stable intercellular adhesion. Migration and wound recovery were enhanced in human keratinocyte monolayers overexpressing ?-opioid receptors in vitro. These ?-opioid receptor effects were antagonized by specific PKC?/? inhibition indicating they were mediated through the PKC signalling pathway. Finally, cells overexpressing ?-opioid receptors developed characteristically long but undirected protrusions containing filamentous actin and ?-opioid receptors, indicating an enhanced migratory phenotype.Opioid receptors affect intercellular adhesion and wound healing mechanisms, underlining the importance of a cutaneous neuroendocrine system in wound healing and skin homeostasis.This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

Dataset Information

?-Catenin-regulated myeloid cell adhesion and migration determine wound healing.

Publications

β-Catenin-regulated myeloid cell adhesion and migration determine wound healing.

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