Abstract
Cutaneous wound healing is a complex process that aims to re-establish the original structure of the skin and its functions. Among other disorders, peripheral neuropathies are known to severely impair wound healing capabilities of the skin, revealing the importance of skin innervation for proper repair. Here, we report that peripheral glia are crucially involved in this process. Using a mouse model of wound healing, combined with in vivo fate mapping, we show that injury activates peripheral glia by promoting de-differentiation, cell-cycle re-entry and dissemination of the cells into the wound bed. Moreover, injury-activated glia upregulate the expression of many secreted factors previously associated with wound healing and promote myofibroblast differentiation by paracrine modulation of TGF-β signalling. Accordingly, depletion of these cells impairs epithelial proliferation and wound closure through contraction, while their expansion promotes myofibroblast formation. Thus, injury-activated glia and/or their secretome might have therapeutic potential in human wound healing disorders.
Highlights
Cutaneous wound healing is a complex process that aims to re-establish the original structure of the skin and its functions
After a dedifferentiation and expansion process, injury-activated glia promote wound contraction and healing. This process is mediated by the secretion of factors enhancing transforming growth factor (TGF)-β signalling, which results in increased myofibroblast formation
Tamoxifen (TM)-mediated activation of CreERT2 in the intact skin of Plp-CreERT2; tdTomato mice led to genetic tracing of peripheral glial cells in nerve bundles (NB) of the reticular dermis, nerve terminals around hair follicles (HFs), as well as in nerve endings between muscle fibres[11,12,13]
Summary
Cutaneous wound healing is a complex process that aims to re-establish the original structure of the skin and its functions. Injury-activated glia upregulate the expression of many secreted factors previously associated with wound healing and promote myofibroblast differentiation by paracrine modulation of TGF-β signalling Depletion of these cells impairs epithelial proliferation and wound closure through contraction, while their expansion promotes myofibroblast formation. Cells expressing the progenitor marker Sox[2] and originating either from nerve terminals around hair follicles (HFs), from injured peripheral nerves or from distant sites outside the regenerating dermis, were shown to be involved in skin wound healing[9]. How these cells contribute to the repair process is not entirely clear. This process is mediated by the secretion of factors enhancing transforming growth factor (TGF)-β signalling, which results in increased myofibroblast formation
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