Deep and voluminous skin wounds are repaired with scars, by mobilization of fibroblasts and extracellular matrix from fascia, deep below the skin. The molecular trigger of this novel repair mechanism is incompletely understood. Here we reveal that the gap junction alpha-1 protein (Connexin43, Cx43) is the key to patch repair of deep wounds. By combining full-thickness wound models with fibroblast lineage specific transgenic lines, we show Cx43 expression is substantially upregulated in specialized fibroblasts of the fascia deep beneath the skin that are responsible for scar formation. Using live imaging of fascia fibroblasts and fate tracing of the fascia extracellular matrix we show that Cx43 inhibition disrupts calcium oscillations in cultured fibroblasts and that this inhibits collective migration of fascia EPFs necessary to mobilize fascia matrix into open wounds. Cell–cell communication through Cx43 thus mediates matrix movement and scar formation, and is necessary for patch repair of voluminous wounds. These mechanistic findings have broad clinical implications toward treating fibrosis, aggravated scarring and impaired wound healing.

通过从皮肤深处的筋膜中动员成纤维细胞和细胞外基质，用疤痕修复深而大的皮肤伤口。这种新型修复机制的分子触发尚不完全清楚。在这里，我们揭示了间隙连接 alpha-1 蛋白（Connexin43、Cx43）是修复深部伤口的关键。通过将全层伤口模型与成纤维细胞谱系特异性转基因株系相结合，我们发现 Cx43 表达在负责疤痕形成的皮肤深处筋膜的特化成纤维细胞中显着上调。使用筋膜成纤维细胞的实时成像和筋膜细胞外基质的命运追踪，我们表明 Cx43 抑制破坏了培养的成纤维细胞中的钙振荡，并且这抑制了动员筋膜基质进入开放性伤口所必需的筋膜 EPF 的集体迁移。因此，通过 Cx43 的细胞间通讯介导了基质运动和疤痕形成，并且对于大量伤口的补片修复是必要的。这些机制发现对治疗纤维化、疤痕加重和伤口愈合受损具有广泛的临床意义。