The Regenerative Potential of Substance P

Redkiewicz, Patrycja

doi:10.3390/ijms23020750

Cited by 14 publications

(9 citation statements)

References 91 publications

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“…The multiple effects of 4-AP treatment, however, suggest that SCs and neurons were not the only components of successful wound healing impacted by this drug. For example, NGF, Substance P and TGF-β levels were all elevated by 4-AP treatment, and each of these has been shown to have pro-reparative effects in skin wound lesions (e.g., (8)(9)(10)(11)(108)(109)(110)(111)(112)(113)). Our in-vitro studies also indicated that 4-AP can have direct effects on keratinocyte migration and expression of SOX10 and NGF by these cells, indicating that the actions of 4-AP are not restricted to neuronal cell types.…”

Section: Discussionmentioning

confidence: 99%

4-aminopyridine promotes accelerated skin wound healing via neurogenic-mediator expression

Guddadarangaiah

Govindappa

Nelson

et al. 2021

Preprint

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The discovery of ways to enhance skin wound healing is of great importance due to the frequency of these lesions. We discovered that 4-aminopyridine (4-AP), a potassium channel blocker, greatly enhances skin wound healing. Benefits include faster wound closure, restoration of normal-appearing skin architecture and epidermal thickness, increased vascularization and increases in K14+ keratinocytes. Hair follicle number was increased, both histologically and by analysis of K15 and K17 expression. Levels of vimentin (which marks fibroblasts) and α-smooth muscle actin (α-SMA, which marks collagen-producing myofibroblasts) increased, as did α-SMA+ cell numbers. 4-AP also increased numbers of axons and S-100+ Schwann cells, and increased expression of p75-NTR and SOX10. Treatment also increased levels of nerve growth factor, transforming growth factor-β, Substance P and PGP9.5, important modulators of wound healing. As 4-AP is already used for treatment of multiple sclerosis and other chronic neurological syndromes, it has strong potential for rapid translational development.

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Section: Discussionmentioning

confidence: 99%

4-aminopyridine promotes accelerated skin wound healing via neurogenic-mediator expression

Guddadarangaiah

Govindappa

Nelson

et al. 2021

Preprint

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“…The half-life of SP is quite short in tissues, ranging from seconds to minutes [ 17 , 36 ]. Once released, SP binds to its receptors and forms a ligand/receptor complex.…”

Section: Overview Of Substance P and Its Receptorsmentioning

confidence: 99%

“…Substance P (SP, with an amino acid sequence of Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met.NH 2 ) was first discovered in 1931 by Von Euler and Gaddum [ 13 ]. Thereafter, many investigations have led to our current understanding that SP functions as an important mediator involved in a wide array of biological processes, including pain signaling, inflammation regulation, host defense response, and wound healing processes [ 14 , 15 , 16 , 17 ]. After its release, SP binds to, and subsequently primes, its functional receptors on the surface of effector cells, through which SP signals to several cellular signaling pathways and, consequently, exerts its multifaceted (patho)physiological functions [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Inflammation and Organ Injury the Role of Substance P and Its Receptors

Zhu

Bhatia

2023

IJMS

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Tightly controlled inflammation is an indispensable mechanism in the maintenance of cellular and organismal homeostasis in living organisms. However, aberrant inflammation is detrimental and has been suggested as a key contributor to organ injury with different etiologies. Substance P (SP) is a neuropeptide with a robust effect on inflammation. The proinflammatory effects of SP are achieved by activating its functional receptors, namely the neurokinin 1 receptor (NK1R) receptor and mas-related G protein-coupled receptors X member 2 (MRGPRX2) and its murine homolog MRGPRB2. Upon activation, the receptors further signal to several cellular signaling pathways involved in the onset, development, and progression of inflammation. Therefore, excessive SP–NK1R or SP–MRGPRX2/B2 signals have been implicated in the pathogenesis of inflammation-associated organ injury. In this review, we summarize our current knowledge of SP and its receptors and the emerging roles of the SP–NK1R system and the SP–MRGPRX2/B2 system in inflammation and injury in multiple organs resulting from different pathologies. We also briefly discuss the prospect of developing a therapeutic strategy for inflammatory organ injury by disrupting the proinflammatory actions of SP via pharmacological intervention.

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“…SP has been investigated in several studies among different species. In humans for example, the role of SP in the immune response [ 28 , 29 ], in wound healing [ 30 ] or its association with cardiovascular disease [ 31 ] has been described. In veterinary medicine, SP as a biomarker for objectifying pain as a stressor has so far been investigated primarily in cattle and has been identified as a suitable parameter in various studies [ 32 , 33 , 34 , 35 ].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Substance P as a New Stress Parameter in Horses in a Stress Model Involving Four Different Stress Levels

Scholler¹,

Zablotski²,

May³

2023

Animals

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Stress has a significant impact on equine welfare. There are some studies on the stress response in horses ridden with tight nosebands, but little is known about other stress parameters than cortisol, which potentially could address an emotional component. In this study, blood samples of a total of 74 warmblood horses were used to establish reference values for plasma substance P (SP) concentrations. Moreover, 16 of these warmblood horses were included in a stress model. Four different stress levels (level 1: horses ridden with loose noseband, level 2: tight noseband, level 3: loose noseband and overground endoscope, level 4: tight noseband and overground endoscope) were applied to evaluate SP as a potential stress parameter in horses. Blood samples were taken at rest (t0) and directly after inducing stress (noseband tightening, insertion of endoscope; t1), as well as after 20 min of riding at all gaits (t2). A ridden horse ethogram was applied and showed that horses in the tight noseband group resorted to other stress-related behavioral issues than horses with loose nosebands. Serum cortisol showed a linear increase concurrent with the increase in stress levels with a significant difference between level 1 and level 4 (p = 0.043), proving that stress factors were adequate to evaluate the stress response, whereas SP did not show a correlation with the stress levels. Furthermore, concentrations of SP differed widely between horses but stayed within more narrow limits in the individual horse. As a conclusion, SP might not be a reliable stress parameter in horses in the applied minor stress model.

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The Regenerative Potential of Substance P

Cited by 14 publications

References 91 publications

4-aminopyridine promotes accelerated skin wound healing via neurogenic-mediator expression

4-aminopyridine promotes accelerated skin wound healing via neurogenic-mediator expression

Inflammation and Organ Injury the Role of Substance P and Its Receptors

Evaluation of Substance P as a New Stress Parameter in Horses in a Stress Model Involving Four Different Stress Levels

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