Interaction of calcitonin gene related peptide (CGRP) and substance P (SP) in human skin

Schlereth, Tanja; Schukraft, Jonas; Krämer-Best, Heidrun H.; Geber, Christian; Ackermann, Tatiana; Birklein, Frank

doi:10.1016/j.npep.2016.06.001

Cited by 55 publications

(42 citation statements)

References 56 publications

(70 reference statements)

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“…Other data concerned with skin innervation and internal microcirculation demonstrate that SP and CGRP are simultaneously released from sensory fibers and could cause short-and long-term vasodilation and plasma extravasation [24]. On the basis of the results of our study, it might be suspected that dose related BPA exposure changes the normal pattern of hepatic www.fhc.viamedica.pl innervation, which could disturb blood and bile flow in the portal area and microcirculation within hepatic sinusoids.…”

Section: Discussionsupporting

confidence: 49%

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

Thoene

Godlewski

Rytel

et al. 2018

Folia Histochem Cytobiol.

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Introduction. Bisphenol A (BPA) is used in the chemical industry for manufacturing plastics which are used as food packaging. Data indicate that BPA is released from such products and is widely present in the environment and the human body. So far, the EFSA and the US FDA have determined "safe" BPA oral exposure levels, and a large amount of data indicates that BPA is harmful even at low-doses. Our previously performed analyses concerning BPA exposure demonstrated the impact of this substance on parasympathetic and peptidergic nerve fibers present within the liver. Therefore, this study concerns BPA exposure and sympathetic intrahepatic innervation in reference to several neuropeptides which modulate neuronal responses: cocaine and amphetamine regulated transcript (CART), galanin (GAL), calcitonin gene-regulated peptide (CGRP) and substance P (SP). Materials and methods. Fifteen young swine at 8 weeks of age were used as experimental models of the juvenile human liver. The pigs were divided into 3 groups and received capsules orally with bisphenol at a dose of 0.05 mg/kg b.w./day; a dose of 0.5 mg/kg b.w./day and placebo capsules as a control. After 28 days of oral BPA intake, the animals were euthanized, perfused with 4% paraformaldehyde (PFA), and livers were collected and fixed in PFA. The cryostat sections were subjected to a routine double-labeling immunofluorescence technique. The primary antibodies were directed against dopamine beta hydroxylase (DbH), which is a marker for sympathetic nerves, and one of the investigated neuropeptides: CART, GAL, CGRP and SP, which co-localized the investigated nerves. Immunoreactive nerves were counted in the liver and the percentage presence of each neuronal combination in particular samples of each experimental group were determined and analyzed statistically. Results. The BPA oral intake at low and ten times higher dosage caused an increase of the number of sympathetic nerve fibers within the porcine liver by 48.6% and 63.7%, respectively. Moreover, BPA exposure caused an increased presence of sympathetic nerve fibers in these two experimental groups, which were co-localized with CART and GAL up to 65.9%/173.2% and 147.4%/126.3%, respectively. At the lower BPA doses of 50 μg/kg b.w./day, the percentages of SP+/DbH+ and CGRP+/DbH+ nerve fibers were similar to the control. 114Michael Thoene et al. However at a ten times higher dose, BPA caused an increased number of SP+/ DbH+ and CGRP+/ DbH+ nerve fibers in the liver, up to 46.4% and 73.5% respectively. Conclusions. BPA caused an increase in the number of sympathetic nerve fibers as well as sympathetic nerve fibers which co-localized with neuropeptides in the porcine liver. The increase in CART and GAL were exceptionally high even at low BPA doses. BPA food contamination may dysregulate liver sympathetic innervation, and thereby may change the oxygenated blood supply, alter metabolism and disrupt the activity of hepatic parenchymal cells.

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Section: Discussionsupporting

confidence: 49%

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

Thoene

Godlewski

Rytel

et al. 2018

Folia Histochem Cytobiol.

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“…39 For example, SP, NGF and VIP can induce the degranulation of mast cells, and promote keratinocyte and endothelial cell hyperproliferation; [40][41][42] CGRP cooperates with SP to induce the vasodilation and various pruritus/pain states. 43 More importantly, the use of neuropeptide receptor antagonist improved the psoriasiform dermatitis in the transgenic KC-Tie2 mouse model, and SP and CGRP receptor agonist administration into denervated mouse skin resumed keratinocyte hyperproliferation in a neuropeptide speci c manner. 6 Secondly, the dynamic neuronal-immune system cross-talk has been implicated in various chronic in ammations.…”

Section: Discussionmentioning

confidence: 99%

The nerve injuries interfere with the development of psoriasis

Qin

Sun

Chen

et al. 2020

Preprint

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BackgroundThe involvement of the nerve in psoriasis development has been suggested by sporadic case or case serial reports.ObjectivesTo provide multiple evidence for the nerve in psoriasis development with a retrospective case review, a literature review and a mouse-based experimental study.MethodsPsoriatic patients who had concomitant nerve injuries and such cases from the literatures were reviewed. And, on wild-type mouse level, unilateral denervation surgery was performed on the dorsal skin before and after the induction of psoriasiform dermatitis, respectively. Lesion visual scores were calculated, and lesion biopsies were taken for hematoxylin-eosin (HE) staining, immunofluorescence analysis, and RNA sequencing & bioinformatics analysis at the time before denervation surgery and the 2nd, 4th, 6th, 8th day after the surgery. ResultsAll clincal cases (20/20) showed that local lesions under the control of injured nerves relieved spontaneously or even cleared/spared, and only about 1/3 experienced partial recurrence. Next, experimental study based on mouse model demonstrated that the unilateral denervation prior to imiquimod application interfered with the enhancement of inflammatory reactions (e.g. adaptive immune response and Th17 cell differentiation pathway) and the induction of ipsilateral psoriasiform dermatitis. On the other hand, the unilateral denervation after the induction of psoriasiform dermatitis promoted the regression of inflammatory reactions (e.g. T cell activation, TNF signaling, and Th17 cell differentiation pathway) and the recovery of ipsilateral dermatitis. ConclusionOur study based on both retrospective clinical case review and wild-type mouse experiments provides multiple evidence for the involvement of the nerve in psoriasis development. Regulation of immune events, including TNF signaling and Th17 cell differentiation, may be one of the mechanisms of the nerve in psoriasis.

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“…In the PNS, CGRP is stored and released together with SP from capsaicin sensitive peripheral afferent neurons and is also a potent vasodilator (van Rossum et al, 1997;Holzer, 1988;Maggi, 1995). Notably, co-application of CGRP and SP to human skin induced long lasting vasodilation in a dose-dependent manner highlighting a synergistic effect of the two neuropeptides (Schlereth et al, 2016). Comparable to NPY, CGRP is found to be expressed outside the neurons in diverse organs such as the kidneys, liver, lungs and prostate (Russwurm et al, 2001).…”

Section: Calcitonin Gene Related Peptide (Cgrp)mentioning

confidence: 99%

Autonomic nerve dysfunction and impaired diabetic wound healing: The role of neuropeptides

Theocharidis

Veves

2020

Autonomic Neuroscience

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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 response. Therefore to fully understand the contribution of autonomic nerve dysfunction in diabetic wound healing it is crucial to explore the implication of neuropeptides. Here, we will discuss recent studies elucidating the role of specific neuropeptides in wound healing.

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Interaction of calcitonin gene related peptide (CGRP) and substance P (SP) in human skin

Cited by 55 publications

References 56 publications

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

Alterations in porcine intrahepatic sympathetic nerves after bisphenol A administration

The nerve injuries interfere with the development of psoriasis

Autonomic nerve dysfunction and impaired diabetic wound healing: The role of neuropeptides

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