ID1/ID3 mediate the contribution of skin fibroblasts to local nerve regeneration through Itga6 in wound repair

Abstract 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...

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Autores principales: Zelin Chen, Gufang Shen, Xu Tan, Langfan Qu, Can Zhang, Le Ma, Peng Luo, Xiaohui Cao, Fan Yang, Yunsheng Liu, Yu Wang, Chunmeng Shi
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Publicado: Wiley 2021
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Acceso en línea:https://doaj.org/article/d3120c3e012040d28cc8d6cfa49b419e
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spelling oai:doaj.org-article:d3120c3e012040d28cc8d6cfa49b419e2021-12-03T12:11:46ZID1/ID3 mediate the contribution of skin fibroblasts to local nerve regeneration through Itga6 in wound repair2157-65802157-656410.1002/sctm.21-0093https://doaj.org/article/d3120c3e012040d28cc8d6cfa49b419e2021-12-01T00:00:00Zhttps://doi.org/10.1002/sctm.21-0093https://doaj.org/toc/2157-6564https://doaj.org/toc/2157-6580Abstract 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.Zelin ChenGufang ShenXu TanLangfan QuCan ZhangLe MaPeng LuoXiaohui CaoFan YangYunsheng LiuYu WangChunmeng ShiWileyarticlefibroblastsnerveregenerationskinMedicine (General)R5-920CytologyQH573-671ENStem Cells Translational Medicine, Vol 10, Iss 12, Pp 1637-1649 (2021)
institution DOAJ
collection DOAJ
language EN
topic fibroblasts
nerve
regeneration
skin
Medicine (General)
R5-920
Cytology
QH573-671
spellingShingle fibroblasts
nerve
regeneration
skin
Medicine (General)
R5-920
Cytology
QH573-671
Zelin Chen
Gufang Shen
Xu Tan
Langfan Qu
Can Zhang
Le Ma
Peng Luo
Xiaohui Cao
Fan Yang
Yunsheng Liu
Yu Wang
Chunmeng Shi
ID1/ID3 mediate the contribution of skin fibroblasts to local nerve regeneration through Itga6 in wound repair
description Abstract 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.
format article
author Zelin Chen
Gufang Shen
Xu Tan
Langfan Qu
Can Zhang
Le Ma
Peng Luo
Xiaohui Cao
Fan Yang
Yunsheng Liu
Yu Wang
Chunmeng Shi
author_facet Zelin Chen
Gufang Shen
Xu Tan
Langfan Qu
Can Zhang
Le Ma
Peng Luo
Xiaohui Cao
Fan Yang
Yunsheng Liu
Yu Wang
Chunmeng Shi
author_sort Zelin Chen
title ID1/ID3 mediate the contribution of skin fibroblasts to local nerve regeneration through Itga6 in wound repair
title_short ID1/ID3 mediate the contribution of skin fibroblasts to local nerve regeneration through Itga6 in wound repair
title_full ID1/ID3 mediate the contribution of skin fibroblasts to local nerve regeneration through Itga6 in wound repair
title_fullStr ID1/ID3 mediate the contribution of skin fibroblasts to local nerve regeneration through Itga6 in wound repair
title_full_unstemmed ID1/ID3 mediate the contribution of skin fibroblasts to local nerve regeneration through Itga6 in wound repair
title_sort id1/id3 mediate the contribution of skin fibroblasts to local nerve regeneration through itga6 in wound repair
publisher Wiley
publishDate 2021
url https://doaj.org/article/d3120c3e012040d28cc8d6cfa49b419e
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