Neuropeptide Substance P Enhances Skin Wound Healing In Vitro and In Vivo under Hypoxia
Pressure ulcers (PUs) or sores are a secondary complication of diabetic neuropathy and traumatic spinal cord injury (SCI). PUs tend to occur in soft tissues located around bony prominences and may heal slowly or not at all. A common mechanism underlying impaired healing of PUs may be dysfunction of...
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MDPI AG
2021-02-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/2/222 |
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| author | Suneel Kumar Yuying Tan Francois Berthiaume |
| author_facet | Suneel Kumar Yuying Tan Francois Berthiaume |
| author_sort | Suneel Kumar |
| collection | DOAJ |
| description | Pressure ulcers (PUs) or sores are a secondary complication of diabetic neuropathy and traumatic spinal cord injury (SCI). PUs tend to occur in soft tissues located around bony prominences and may heal slowly or not at all. A common mechanism underlying impaired healing of PUs may be dysfunction of the local neurovascular system including deficiency of essential neuropeptides, such as substance P (SP). Previous studies indicate that disturbance in cutaneous sensory innervation leads to a defect in all stages of wound healing, as is the case after SCI. It is hypothesized that nerve fibers enhance wound healing by promoting initial inflammation via the releasing of neuropeptides such as SP. Therefore, we investigated whether exogenous SP improves skin wound healing using in vitro and in vivo models. For in vitro studies, the effects of SP on keratinocyte proliferation and wound closure after a scratch injury were studied under normoxia (pO<sub>2</sub> ~21%) or hypoxia (pO<sub>2</sub> ~1%) and in presence of normal serum (10% <i>v</i>/<i>v</i>) or low serum (1% <i>v</i>/<i>v</i>) concentrations. Hypoxia and low serum both significantly slowed cell proliferation and wound closure. Under combined low serum and hypoxia, used to mimic the nutrient- and oxygen-poor environment of chronic wounds, SP (10<sup>−7</sup> M) significantly enhanced cell proliferation and wound closure rate. For in vivo studies, two full-thickness excisional wounds were created with a 5 mm biopsy punch on the dorsum on either side of the midline of 15-week-old C57BL/6J male and female mice. Immediately, wounds were treated topically with one dose of 0.5 μg SP or PBS vehicle. The data suggest a beneficial role in wound closure and reepithelization, and thus enhanced wound healing, in male and female mice. Taken together, exogenously applied neuropeptide SP enhanced wound healing via cell proliferation and migration in vitro and in vivo. Thus, exogenous SP may be a useful strategy to explore further for treating PUs in SCI and diabetic patients. |
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| spelling | doaj.art-b7313ad1729f43cb859a705ed5612a5d2023-12-11T17:55:10ZengMDPI AGBiomedicines2227-90592021-02-019222210.3390/biomedicines9020222Neuropeptide Substance P Enhances Skin Wound Healing In Vitro and In Vivo under HypoxiaSuneel Kumar0Yuying Tan1Francois Berthiaume2Department of Biomedical Engineering, Rutgers, State University of New Jersey, 599 Taylor Road, Piscataway, NJ 08854, USADepartment of Biomedical Engineering, Rutgers, State University of New Jersey, 599 Taylor Road, Piscataway, NJ 08854, USADepartment of Biomedical Engineering, Rutgers, State University of New Jersey, 599 Taylor Road, Piscataway, NJ 08854, USAPressure ulcers (PUs) or sores are a secondary complication of diabetic neuropathy and traumatic spinal cord injury (SCI). PUs tend to occur in soft tissues located around bony prominences and may heal slowly or not at all. A common mechanism underlying impaired healing of PUs may be dysfunction of the local neurovascular system including deficiency of essential neuropeptides, such as substance P (SP). Previous studies indicate that disturbance in cutaneous sensory innervation leads to a defect in all stages of wound healing, as is the case after SCI. It is hypothesized that nerve fibers enhance wound healing by promoting initial inflammation via the releasing of neuropeptides such as SP. Therefore, we investigated whether exogenous SP improves skin wound healing using in vitro and in vivo models. For in vitro studies, the effects of SP on keratinocyte proliferation and wound closure after a scratch injury were studied under normoxia (pO<sub>2</sub> ~21%) or hypoxia (pO<sub>2</sub> ~1%) and in presence of normal serum (10% <i>v</i>/<i>v</i>) or low serum (1% <i>v</i>/<i>v</i>) concentrations. Hypoxia and low serum both significantly slowed cell proliferation and wound closure. Under combined low serum and hypoxia, used to mimic the nutrient- and oxygen-poor environment of chronic wounds, SP (10<sup>−7</sup> M) significantly enhanced cell proliferation and wound closure rate. For in vivo studies, two full-thickness excisional wounds were created with a 5 mm biopsy punch on the dorsum on either side of the midline of 15-week-old C57BL/6J male and female mice. Immediately, wounds were treated topically with one dose of 0.5 μg SP or PBS vehicle. The data suggest a beneficial role in wound closure and reepithelization, and thus enhanced wound healing, in male and female mice. Taken together, exogenously applied neuropeptide SP enhanced wound healing via cell proliferation and migration in vitro and in vivo. Thus, exogenous SP may be a useful strategy to explore further for treating PUs in SCI and diabetic patients.https://www.mdpi.com/2227-9059/9/2/222neuropeptidessubstance Pnormoxiahypoxiastarvationproliferation and migration |
| spellingShingle | Suneel Kumar Yuying Tan Francois Berthiaume Neuropeptide Substance P Enhances Skin Wound Healing In Vitro and In Vivo under Hypoxia Biomedicines neuropeptides substance P normoxia hypoxia starvation proliferation and migration |
| title | Neuropeptide Substance P Enhances Skin Wound Healing In Vitro and In Vivo under Hypoxia |
| title_full | Neuropeptide Substance P Enhances Skin Wound Healing In Vitro and In Vivo under Hypoxia |
| title_fullStr | Neuropeptide Substance P Enhances Skin Wound Healing In Vitro and In Vivo under Hypoxia |
| title_full_unstemmed | Neuropeptide Substance P Enhances Skin Wound Healing In Vitro and In Vivo under Hypoxia |
| title_short | Neuropeptide Substance P Enhances Skin Wound Healing In Vitro and In Vivo under Hypoxia |
| title_sort | neuropeptide substance p enhances skin wound healing in vitro and in vivo under hypoxia |
| topic | neuropeptides substance P normoxia hypoxia starvation proliferation and migration |
| url | https://www.mdpi.com/2227-9059/9/2/222 |
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