Connexin43 gap junction drives fascia mobilization and repair of deep skin wounds
| Autor: | Pushkar Ramesh, Yuval Rinkevich, Haifeng Ye, Li Wan, Donovan Correa-Gallegos, Shaohua Zhu, Thomas Volz, Juliane Wannemacher, Jiakuan Zhao, Dongsheng Jiang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Scars Mice Transgenic Cell Communication Matrix (biology) Extracellular matrix 03 medical and health sciences Mice 0302 clinical medicine Live cell imaging Fibrosis medicine Animals Humans Fascia Fibroblast Molecular Biology Wound Healing integumentary system business.industry Gap junction medicine.disease Cell biology Extracellular Matrix body regions Disease Models Animal 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Connexin 43 NIH 3T3 Cells Calcium medicine.symptom business |
| Zdroj: | Matrix biology : journal of the International Society for Matrix Biology. 97 |
| ISSN: | 1569-1802 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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