Penuela Silvia, Kelly John J, Churko Jared M, Barr Kevin J, Berger Amy C, Laird Dale W
Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada.
Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario, Canada.
J Invest Dermatol. 2014 Jul;134(7):2026-2035. doi: 10.1038/jid.2014.86. Epub 2014 Feb 12.
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 α-smooth muscle actin expression in response to TGF-β, 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.
泛连接蛋白1（Panx1）是一种形成通道的糖蛋白，在新生小鼠皮肤中表达，但在老年小鼠皮肤中不表达。对Panx1基因敲除（KO）小鼠皮肤进行组织学染色显示，表皮和真皮厚度减少，皮下脂肪组织增加。在背部皮肤进行打孔活检后，突变小鼠的伤口愈合明显延迟。划痕伤口和增殖试验表明，与对照组相比，来自KO小鼠的培养角质形成细胞迁移能力更强，而真皮成纤维细胞增殖能力更强。此外，接种有KO小鼠成纤维细胞的胶原凝胶收缩明显减少，与用Panx1阻滞剂丙磺舒处理的野生型成纤维细胞相当。与伤口收缩过程中分化的野生型肌成纤维细胞不同，KO成纤维细胞对转化生长因子-β没有增加α-平滑肌肌动蛋白的表达。我们得出结论，Panx1在皮肤发育早期控制角质形成细胞和真皮成纤维细胞的细胞特性，并在损伤时调节伤口修复。
