Neuropeptide Substance P Enhances Skin Wound Healing In Vitro and In Vivo under Hypoxia.

Published on Feb 22, 2021in Biomedicines4.717
· DOI :10.3390/BIOMEDICINES9020222
Suneel Kumar18
Estimated H-index: 18
Yuying Tan5
Estimated H-index: 5
Francois Berthiaume53
Estimated H-index: 53
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 (pO2 ~21%) or hypoxia (pO2 ~1%) and in presence of normal serum (10% v/v) or low serum (1% v/v) 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 (10−7 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.
#1Bo Young Chung (Sacred Heart Hospital)H-Index: 12
#2Han Bi Kim (Sacred Heart Hospital)H-Index: 1
Last. Hye One Kim (Sacred Heart Hospital)H-Index: 14
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Post-burn pruritus is the pruritus that occurs after burn during the rehabilitation and healing process of burn wounds. The post-burn pruritus is a common and serious complication of burn injury, which severely lowers the quality of life of the patient. Many potential treatments are available for pruritus but there is no consensus of the best single treatment yet. The precise mechanism of post-burn pruritus has not been elucidated, but it appears to have pruritogenic and neuropathic aspects. Cli...
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#1Marta Kopcewicz (PAN: Polish Academy of Sciences)H-Index: 6
#2Katarzyna Walendzik (PAN: Polish Academy of Sciences)H-Index: 4
Last. Barbara Gawronska-Kozak (PAN: Polish Academy of Sciences)H-Index: 19
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Since there are limited studies analyzing the impact of age, sex and obesity on cutaneous repair, the current study evaluated excisional skin wound healing as a function of age, sex and diet in C57BL/6 mice subjected to either low (LFD) or high (HFD) fat diet. Older mice accumulated increased body fat relative to younger mice under HFD. Skin wound healing at particular stages was affected by age in the aspect of Tgfbeta-1, MCP-1, Mmp-9 and Mmp-13 expression. The most profound, cumulative effect ...
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#1Jinyeong Yu (Kyung Hee University)H-Index: 5
#2Donghyun Nam (Kyung Hee University)H-Index: 3
Last. Ki-Sook Park (Kyung Hee University)H-Index: 18
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Abstract Diabetes induces cellular dysfunction in dermal fibroblasts, such as impairment in migration, which is a major cause of chronic wound. Here, we demonstrated that the migration of human dermal fibroblasts was impaired under a high glucose culture condition. Substance P (SP) rescued the impaired migration of the fibroblasts. The activity of Rac1, Rho-associated kinase (ROCK), and Src was required for SP-mediated rescue of fibroblast migration. SP activated Rac1 and Src, whereas, NSC23766,...
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#1Wilai Kosol (RU: Rutgers University)H-Index: 1
#2Suneel Kumar (RU: Rutgers University)H-Index: 18
Last. Francois Berthiaume (RU: Rutgers University)H-Index: 53
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Abstract Chronic wounds, such as pressure ulcers, are a common complication of impaired peripheral circulation, such as in advanced diabetes. Factors secreted by mesenchymal stromal cells (MSCs) have been shown to enhance wound healing in vitro and in vivo. However, there is little understanding of the impact of the chronic wound environment, namely the limited supply of nutrients and oxygen, on the ability of wound cells to respond to MSCs. In this study, we first established the effects of hyp...
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#1Georgios Theocharidis (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 6
#2Aristidis Veves (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 76
Abstract Lower extremity ulcerations represent a major complication in diabetes mellitus and involve multiple physiological factors that lead to impairment of wound healing. Neuropeptides are neuromodulators implicated in various processes including diabetic wound healing. Diabetes causes autonomic and small sensory nerve fibers neuropathy as well as inflammatory dysregulation, which manifest with decreased neuropeptide expression and a disproportion in pro- and anti- inflammatory cytokine respo...
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#1David M. Brienza (University of Pittsburgh)H-Index: 26
#2Shilpa Krishnan (UTMB: University of Texas Medical Branch)H-Index: 8
Last. Ana Luiza Caltabiano Allegretti (University of Texas Health Science Center at San Antonio)H-Index: 5
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Predictors of pressure ulcer incidence following traumatic spinal cord injury: a secondary analysis of a prospective longitudinal study
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#1Susmit Suvas (WSU: Wayne State University)H-Index: 23
Substance P (SP) is an undecapeptide present in the CNS and the peripheral nervous system. SP released from the peripheral nerves exerts its biological and immunological activity via high-affinity neurokinin 1 receptor (NK1R). SP is also produced by immune cells and acts as an autocrine or paracrine fashion to regulate the function of immune cells. In addition to its proinflammatory role, SP and its metabolites in combination with insulin-like growth factor-1 are shown to promote the corneal epi...
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#1Jihyun Um (Kyung Hee University)H-Index: 6
#2Jinyeong Yu (Kyung Hee University)H-Index: 5
Last. Ki-Sook Park (Kyung Hee University)H-Index: 18
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: Wound healing is delayed in diabetes due to a number of factors, including impaired angiogenesis and poor dermal healing. The present study demonstrated that subcutaneous administration of substance P (SP) accelerates wound healing in db/db type 2 diabetic mice (db/db mice). SP injection (10 nM/kg, subcutaneously) enhanced angiogenesis, induced the mobilization of endothelial progenitor cells (EPCs) and increased the number of EPC‑colony forming units (EPC‑CFUs) in the bone marrow of db/db mic...
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#1Tao NiH-Index: 4
#2Yushu LiuH-Index: 2
Last. Min Yao (SJTU: Shanghai Jiao Tong University)H-Index: 1
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Purpose: Delayed wound healing is an intractable complex of diabetes and substance P (SP) is proved to benefit wound healing, whose functioning mechanism remains elusive. This study aims at revealing whether the influence of SP on diabetic wound healing is dependent on inflammatory responses, particularly NF-κB. Methods: Skin fibroblasts of genetically diabetic mice were co-cultured with bone marrow-derived macrophages, and treated with SP, SP + L703,606 (a neurokinin-1 receptor antagonist), or ...
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#1Ju Hyeong Park (Kyung Hee University)H-Index: 3
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Diabetic ulceration is one of the most debilitating complications of diabetes and is the main cause of amputation. The diabetic environment is characterized by prolonged inflammation and abnormal angiogenesis, leading to delayed wound healing. Thus, regulation of inflammation and neovascularization is considered a desirable target for diabetes. The critical purpose of this study was to determine whether systemically administered Substance P (SP) could promote wound healing in diabetic environmen...
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