Topically applied substance P enhanced healing of open excision wound in rats

Kant, Vinay; Gopal, Anu; Kumar, Dhirendra; Bag, Sadhan; Kurade, N. P.; Kumar, Amit; Tandan, Surendra K.; Kumar, Dinesh

doi:10.1016/j.ejphar.2013.04.042

Cited by 55 publications

(55 citation statements)

References 59 publications

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“…10e12 SP promotes wound healing in nondiabetic and diabetic corneal wounds that mainly involve epithelial cells 13,14 and in nondiabetic cutaneous wounds. 15,16 However, there is little information regarding its effect in diabetic skin wounds that are characterized by chronic inflammation, neuroischemia, and increased expression of MMPs that degrade proteins, including growth factors. 4 During normal wound healing, macrophages demonstrate transitions in phenotype and function in tissue repair progression, although the factors that regulate these transitions remain poorly defined.…”

mentioning

confidence: 99%

Substance P Promotes Wound Healing in Diabetes by Modulating Inflammation and Macrophage Phenotype

Leal

Carvalho

Tellechea

et al. 2015

The American Journal of Pathology

174

155

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Diabetic foot ulceration is a major complication of diabetes. Substance P (SP) is involved in wound healing, but its effect in diabetic skin wounds is unclear. We examined the effect of exogenous SP delivery on diabetic mouse and rabbit wounds. We also studied the impact of deficiency in SP or its receptor, neurokinin-1 receptor, on wound healing in mouse models. SP treatment improved wound healing in mice and rabbits, whereas the absence of SP or its receptor impaired wound progression in mice. Moreover, SP bioavailability in diabetic skin was reduced as SP gene expression was decreased, whereas the gene expression and protein levels of the enzyme that degrades SP, neutral endopeptidase, were increased. Diabetes and SP deficiency were associated with absence of an acute inflammatory response important for wound healing progression and instead revealed a persistent inflammation throughout the healing process. SP treatment induced an acute inflammatory response, which enabled the progression to the proliferative phase and modulated macrophage activation toward the M2 phenotype that promotes wound healing. In conclusion, SP treatment reverses the chronic proinflammatory state in diabetic skin and promotes healing of diabetic wounds. (Am J Pathol 2015 http://dx

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mentioning

confidence: 99%

Substance P Promotes Wound Healing in Diabetes by Modulating Inflammation and Macrophage Phenotype

Leal

Carvalho

Tellechea

et al. 2015

The American Journal of Pathology

174

155

View full text Add to dashboard Cite

show abstract

“…IL-10 ( [38,39] and TGF-b [40] also possess anti-inflammatory activity and SP has been shown to increase TGF-b [11] and IL-10 [11,41] expressions/levels. Moreover, H & E staining evidently showed that SP markedly and progressively reduce the inflammatory cells at wound site until day 19, as compared to control and gel-treated group (Fig.…”

Section: Discussionmentioning

confidence: 98%

“…SP has been shown to promote cutaneous wound healing in non-diabetic rats [11,16]. Topical application of SP (10 À7 M) enhanced wound closure in nitric oxide synthase knock out mice and non-diabetic rats [5,11]. In addition, exogenously administration of SP stimulated fibroblast http proliferation, angiogenesis and collagen organization during Achilles tendon healing in rats [13].…”

Section: Introductionmentioning

confidence: 98%

“…The reduction of SP directly contributes to the abnormal healing response in patients with diabetes [15]. SP has been shown to promote cutaneous wound healing in non-diabetic rats [11,16]. Topical application of SP (10 À7 M) enhanced wound closure in nitric oxide synthase knock out mice and non-diabetic rats [5,11].…”

Section: Introductionmentioning

confidence: 98%

“…SP, a 10-amino acid neuropeptide, is released by the sensory nerve fibers during tissue insult and has been reported to be a mediator of inflammation in wound healing [6]. It binds to neurokinin-1 (NK-1) receptors and elicits vasodilatory action via nitric oxide, alters vascular permeability and enhances the delivery and accumulation of leukocytes to tissues for the expression of the local immune response [7], SP stimulates the production of various cytokines such as, tumor necrosis factor-alpha (TNF-a), interleukin-1beta (IL-1b), IL-2, IL-8 and IL-6, and growth factors namely, vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGF-b 1 ), involved in wound healing [8][9][10][11]. It is also involved in the angiogenesis, epidermal cell proliferation, and capillary and fibroblast proliferation [12,13].…”

Section: Introductionmentioning

confidence: 99%

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