Panx1 Regulates Cellular Properties of Keratinocytes and Dermal Fibroblasts in Skin Development and Wound Healing

被引:59
作者
Penuela, Silvia [1 ]
Kelly, John J. [1 ]
Churko, Jared M. [1 ]
Barr, Kevin J. [2 ]
Berger, Amy C. [2 ]
Laird, Dale W. [1 ,2 ]
机构
[1] Univ Western Ontario, Dept Anat & Cell Biol, London, ON N6A 5C1, Canada
[2] Univ Western Ontario, London, ON N6A 5C1, Canada
基金
加拿大健康研究院;
关键词
GAP-JUNCTION PROTEINS; PANNEXIN; ATP RELEASE; DIFFERENTIATION; CHANNELS; ACTIVATION; HEMICHANNELS; CONTRACTION; MEMBRANE; FAMILY;
D O I
10.1038/jid.2014.86
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Pannexin1 (Panx1), a channel-forming glycoprotein is expressed in neonatal but not in aged mouse skin. Histological staining of Panx1 knockout (KO) mouse skin revealed a reduction in epidermal and dermal thickness and an increase in hypodermal adipose tissue. Following dorsal skin punch biopsies, mutant mice exhibited a significant delay in wound healing. Scratch wound and proliferation assays revealed that cultured keratinocytes from KO mice were more migratory, whereas dermal fibroblasts were more proliferative compared with controls. In addition, collagen gels populated with fibroblasts from KO mice exhibited significantly reduced contraction, comparable to WT fibroblasts treated with the Panx1 blocker, probenecid. KO fibroblasts did not increase a,smooth muscle actin expression in response to TGF-beta, as is the case for differentiating WT myofibroblasts during wound contraction. We conclude that Panx1 controls cellular properties of keratinocytes and dermal fibroblasts during early stages of skin development and modulates wound repair upon injury.
引用
收藏
页码:2026 / 2035
页数:10
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