Molecular Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, 20892, USA.
Division of Operative Dentistry, Department of Restorative Dentistry, Tohoku University, Graduate School of Dentistry 4-1, Seiryo chou, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
Sci Rep. 2021 Jan 19;11(1):1779. doi: 10.1038/s41598-021-81074-1.
Pannexin 3 (Panx3), a member of the gap junction pannexin family is required for the development of hard tissues including bone, cartilage and teeth. However, the role of Panx3 in skin development remains unclear. Here, we demonstrate that Panx3 regulates skin development by modulating the transcription factor, Epiprofin (Epfn). Panx3 mice have impaired skin development and delayed hair follicle regeneration. Loss of Panx3 in knockout mice and suppression by shRNA both elicited a reduction of Epfn expression in the epidermis. In cell culture, Panx3 overexpression promoted HaCaT cell differentiation, cell cycle exit and enhanced Epfn expression. Epfn mice and inhibition of Epfn by siRNA showed no obvious differences of Panx3 expression. Furthermore, Panx3 promotes Akt/NFAT signaling pathway in keratinocyte differentiation by both Panx3 ATP releasing channel and ER Ca channel functions. Our results reveal that Panx3 has a key role factor for the skin development by regulating Epfn.
连接蛋白 3(Panx3)是间隙连接连接蛋白家族的成员,对于包括骨骼、软骨和牙齿在内的硬组织的发育是必需的。然而,Panx3 在皮肤发育中的作用尚不清楚。在这里,我们证明 Panx3 通过调节转录因子 Epiprofin(Epfn)来调节皮肤发育。Panx3 小鼠的皮肤发育受损,毛囊再生延迟。敲除小鼠中 Panx3 的缺失和 shRNA 的抑制都导致表皮中 Epfn 表达减少。在细胞培养中,Panx3 的过表达促进了 HaCaT 细胞的分化、细胞周期退出和 Epfn 表达的增强。Epfn 小鼠和 siRNA 抑制 Epfn 表达没有明显改变 Panx3 的表达。此外,Panx3 通过 Panx3 ATP 释放通道和 ER Ca 通道功能促进角质形成细胞分化中的 Akt/NFAT 信号通路。我们的结果表明,Panx3 通过调节 Epfn 是皮肤发育的关键调节因子。