The biological effects and mechanisms of calcitonin gene-related peptide on human endothelial cell

Tuo, Yonghua; Guo, Xiaolei; Zhang, Xinxin; Wang, Zhao; Zhou, Jian; Xia, Liheng; Zhang, Yongtao; Wen, Jianbo; Jin, Dayong

doi:10.3109/10799893.2013.770528

Cited by 55 publications

(49 citation statements)

References 29 publications

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“…Perhaps, the CGRP receptors located on the endothelium of human subcutaneous arteries have different biological effects than being directly involved in the vasomotor control or the density of CGRP receptors are significantly higher on smooth muscle cells compared with the endothelium. Recent studies have shown that CGRP acts as a pro-angiogenic growth factor by increasing the secretion of vascular endothelial growth factor and expression of focal adhesion kinase (Tuo et al 2013), thereby contributing to remodelling.…”

Section: Discussionmentioning

confidence: 99%

Differential localization and characterization of functional calcitonin gene-related peptide receptors in human subcutaneous arteries

et al. 2014

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The present results indicate that CGRP exerts its vasodilatory effect in human subcutaneous arteries by binding to its receptors located on the smooth muscle cells and is suggested to be endothelium-independent. In conclusion, these results underline the dynamic distribution of CGRP receptor components in the human circulation reflecting the important role of CGRP in fine tuning of the blood flow in resistance arteries.

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Section: Discussionmentioning

confidence: 99%

Differential localization and characterization of functional calcitonin gene-related peptide receptors in human subcutaneous arteries

et al. 2014

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“…SP and CGRP are neuropeptides found within dorsal root ganglia neurons and C-fibres of sensory neurons, ultimately involved in the facilitation of pain perception within the peripheral and central nervous system. In addition, CGRP has been shown to induce proliferation of endothelial cells [53], suggesting that expression by NP cells could also induce the angiogenesis seen in disc degeneration. Here, we demonstrate that SP is produced by NP cells and was seen in more degenerate samples than nondegenerate NP samples, with levels increasing in infiltrated discs compared with degenerate discs.…”

Section: Discussionmentioning

confidence: 99%

Expression and regulation of neurotrophic and angiogenic factors during human intervertebral disc degeneration

et al. 2014

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IntroductionThe degenerate intervertebral disc (IVD) becomes innervated by sensory nerve fibres, and vascularised by blood vessels. This study aimed to identify neurotrophins, neuropeptides and angiogenic factors within native IVD tissue and to further investigate whether pro-inflammatory cytokines are involved in the regulation of expression levels within nucleus pulposus (NP) cells, nerve and endothelial cells.MethodsQuantitative real-time PCR (qRT-PCR) was performed on 53 human IVDs from 52 individuals to investigate native gene expression of neurotrophic factors and their receptors, neuropeptides and angiogenic factors. The regulation of these factors by cytokines was investigated in NP cells in alginate culture, and nerve and endothelial cells in monolayer using RT-PCR and substance P (SP) protein expression in interleukin-1 (IL-1β) stimulated NP cells.ResultsInitial investigation on uncultured NP cells identified expression of all neurotrophins by native NP cells, whilst the nerve growth factor (NGF) receptor was only identified in severely degenerate and infiltrated discs, and brain derived neurotrophic factor (BDNF) receptor expressed by more degenerate discs. BDNF expression was significantly increased in infiltrated and degenerate samples. SP and vascular endothelial growth factor (VEGF) were higher in infiltrated samples. In vitro stimulation by IL-1β induced NGF in NP cells. Neurotropin-3 was induced by tumour necrosis factor alpha in human dermal microvascular endothelial cells (HDMECs). SP gene and protein expression was increased in NP cells by IL-1β. Calcitonin gene related peptide was increased in SH-SY5Y cells upon cytokine stimulation. VEGF was induced by IL-1β and interleukin-6 in NP cells, whilst pleiotrophin was decreased by IL-1β. VEGF and pleiotrophin were expressed by SH-SY5Y cells, and VEGF by HDMECs, but were not modulated by cytokines.ConclusionsThe release of cytokines, in particular IL-1β during IVD degeneration, induced significant increases in NGF and VEGF which could promote neuronal and vascular ingrowth. SP which is released into the matrix could potentially up regulate the production of matrix degrading enzymes and also sensitise nerves, resulting in nociceptive transmission and chronic low back pain. This suggests that IL-1β is a key regulatory cytokine, involved in the up regulation of factors involved in innervation and vascularisation of tissues.

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“…CGRP-containing primary sensory neurons play an important role in epidermal homeostasis, vasoregulation, inflammation, nociception and potent vasodilation [13][14][15]. CGRP can promote proliferation and migration of endothelial cells [16]. It has also reported that keratinocytes could express CGRP to implicate for neuropathic and inflammatory pain [13].…”

Section: Introductionmentioning

confidence: 99%

Calcitonin gene-related peptide cooperates with substance P to inhibit melanogenesis and induces apoptosis of B16F10 cells

et al. 2015

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The biological effects and mechanisms of calcitonin gene-related peptide on human endothelial cell

Cited by 55 publications

References 29 publications

Differential localization and characterization of functional calcitonin gene-related peptide receptors in human subcutaneous arteries

Differential localization and characterization of functional calcitonin gene-related peptide receptors in human subcutaneous arteries

Expression and regulation of neurotrophic and angiogenic factors during human intervertebral disc degeneration

Calcitonin gene-related peptide cooperates with substance P to inhibit melanogenesis and induces apoptosis of B16F10 cells

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