ID1/ID3 mediate the contribution of skin fibroblasts to local nerve regeneration through Itga6 in wound repair
| Autor: | Xiaohui Cao, Peng Luo, Xu Tan, Gufang Shen, Langfan Qu, Zelin Chen, Yu Wang, Fan Yang, Can Zhang, Chunmeng Shi, Le Ma, Yunsheng Liu |
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| Rok vydání: | 2021 |
| Předmět: |
Inhibitor of Differentiation Protein 1
Medicine (General) Cell type skin nerve Integrin alpha6 Manufacturing for Regenerative Medicine R5-920 Downregulation and upregulation Peripheral Nerve Injuries Medicine Humans Axon Wound Healing QH573-671 integumentary system business.industry Regeneration (biology) Cell Biology General Medicine Sciatic nerve injury Fibroblasts medicine.disease Tissue Specific Stem Cells Cell biology Neoplasm Proteins Nerve Regeneration Transplantation medicine.anatomical_structure regeneration Axon guidance Inhibitor of Differentiation Proteins Sciatic Neuropathy Cytology business Wound healing Developmental Biology |
| Zdroj: | Stem Cells Translational Medicine Stem Cells Translational Medicine, Vol 10, Iss 12, Pp 1637-1649 (2021) |
| ISSN: | 2157-6580 |
| Popis: | Cutaneous wound healing requires intricate synchronization of several key processes. Among them, local nerve regeneration is known to be vitally important for proper repair. However, the underlying mechanisms of local nerve regeneration are still unclear. Fibroblasts are one of the key cell types within the skin whose role in local nerve regeneration has not been extensively studied. In our study, we found skin fibroblasts were in tight contact with regenerated nerves during wound healing, while rare interactions were shown under normal circumstances. Moreover, skin fibroblasts surrounding the nerves were shown to be activated and reprogrammed to exhibit neural cell‐like properties by upregulated expressing inhibitor of DNA binding 1 (ID1) and ID3. Furthermore, we identified the regulation of integrin α6 (Itga6) by ID1/ID3 in fibroblasts as the mechanism for axon guidance. Accordingly, transplantation of the ID1/ID3‐overexpressing fibroblasts or topical injection of ID1/ID3 lentivirus significantly promoted local nerve regeneration and wound healing following skin excision or sciatic nerve injury. Therefore, we demonstrated a new role for skin fibroblasts in nerve regeneration following local injury by directly contacting and guiding axon regrowth, which might hold therapeutic potential in peripheral nerve disorders and peripheral neuropathies in relatively chronic refractory wounds. Skin fibroblasts contribute to local nerve regeneration by directly guiding axon regrowth, which suggests a potential therapeutic strategy for peripheral nerve disorders and relatively chronic refractory wounds. |
| Databáze: | OpenAIRE |
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