Calcitonin gene-related peptide alleviates hypertrophic scar formation by inhibiting the inflammation

Zhou, Yu; Hua, Tianfeng; Weng, Xiaojuan; Ma, Dameng; Li, Xiaojing

doi:10.1007/s00403-020-02179-7

Cited by 8 publications

(12 citation statements)

References 27 publications

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“…Macrophages could change the extracellular makeup on the dura following polarization from neuropeptides or cytokines. in vitro work shows that CGRP shifts either LPS-treated macrophages or tissue damage macrophages toward an M2 tissue-remodeling phenotype ( 65 , 97 ). Changes to the interaction of the TG endings and the dura superstructure could potentially cause dysregulated firing via mechanoreceptors.…”

Section: Discussionmentioning

confidence: 99%

“…CGRP also acts on resident immune cells such as macrophages and mast cells. The macrophages may become activated, and the mast cells degranulate ( 65 , 66 ). This degranulation involves release of inflammatory chemicals such as histamine, proteases and various cytokines that are implicated in headache ( 67 ).…”

Section: Dura Mater Relevance and Overviewmentioning

confidence: 99%

“…The B cells can produce antibodies against the antigens, and the T cells can differentiate to either kill cells or aid fellow B and T cells for enhanced immune response. Most of the work of CGRP's effect on these cells has been done in culture, but it appears that CGRP induces neurogenic inflammation through mast cell degranulation, while enhancing anti-inflammatory macrophage function when stimulated with an inflammatory compound ( 27 , 65 , 66 , 74 ). CGRP appears to reduce dendritic cell presentation of antigens ( 75 ).…”

Section: Dura Mater Relevance and Overviewmentioning

confidence: 99%

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Dural Immune Cells, CGRP, and Migraine

Balcziak

Russo

2022

Front. Neurol.

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Migraine is the most common neurological disorder in the world, affecting 12% of the population. Migraine involves the central nervous system, trigeminal nerves and meninges. Recent advances have shown that targeting calcitonin gene-related peptide (CGRP) through either antibodies or small molecule receptor antagonists is effective at reducing episodic and chronic migraine episodes, but these therapeutics are not effective in all patients. This suggests that migraine does not have a singular molecular cause but is likely due to dysregulated physiology of multiple mechanisms. An often-overlooked part of migraine is the potential involvement of the immune system. Clinical studies have shown that migraine patients may have dysregulation in their immune system, with abnormal plasma cytokine levels either during the attack or at baseline. In addition, those who are immunocompromised appear to be at a higher risk of migraine-like disorders. A recent study showed that migraine caused changes to transcription of immune genes in the blood, even following treatment with sumatriptan. The dura mater is densely packed with macrophages, mast and dendritic cells, and they have been found to associate with meningeal blood vessels and trigeminal afferent endings. Recent work in mice shows activation and morphological changes of these cells in rodents following the migraine trigger cortical spreading depression. Importantly, each of these immune cell types can respond directly to CGRP. Since immune cells make up a large portion of the dura, have functional responses to CGRP, and interact with trigeminal afferents, CGRP actions on the dural immune system are likely to play key roles in migraine.

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Section: Discussionmentioning

confidence: 99%

Section: Dura Mater Relevance and Overviewmentioning

confidence: 99%

Section: Dura Mater Relevance and Overviewmentioning

confidence: 99%

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Dural Immune Cells, CGRP, and Migraine

Balcziak

Russo

2022

Front. Neurol.

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“…The dura mater contains extracerebral blood vessels, fibroblasts, trigeminal afferent endings, and numerous immune cells ( Erdener et al, 2021 ). After peripheral nerve action and the release of CGRP, SP, and PACAP, macrophages may become activated, and mast cells degranulate ( Manning et al, 2016 ; Zhou et al, 2022 ). The production of inflammatory substances during degranulation, including histamine, proteases, and cytokines, is thought to contribute to headaches ( Levy et al, 2007 ).…”

Section: Basic Study Status and Mechanism Of Acupuncture Protecting F...mentioning

confidence: 99%

Therapeutic applications and potential mechanisms of acupuncture in migraine: A literature review and perspectives

Chen

Liu²,

Song³

et al. 2022

Front. Neurosci.

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Acupuncture is commonly used as a treatment for migraines. Animal studies have suggested that acupuncture can decrease neuropeptides, immune cells, and proinflammatory and excitatory neurotransmitters, which are associated with the pathogenesis of neuroinflammation. In addition, acupuncture participates in the development of peripheral and central sensitization through modulation of the release of neuronal-sensitization-related mediators (brain-derived neurotrophic factor, glutamate), endocannabinoid system, and serotonin system activation. Clinical studies have demonstrated that acupuncture may be a beneficial migraine treatment, particularly in decreasing pain intensity, duration, emotional comorbidity, and days of acute medication intake. However, specific clinical effectiveness has not been substantiated, and the mechanisms underlying its efficacy remain obscure. With the development of biomedical and neuroimaging techniques, the neural mechanism of acupuncture in migraine has gained increasing attention. Neuroimaging studies have indicated that acupuncture may alter the abnormal functional activity and connectivity of the descending pain modulatory system, default mode network, thalamus, frontal-parietal network, occipital-temporal network, and cerebellum. Acupuncture may reduce neuroinflammation, regulate peripheral and central sensitization, and normalize abnormal brain activity, thereby preventing pain signal transmission. To summarize the effects and neural mechanisms of acupuncture in migraine, we performed a systematic review of literature about migraine and acupuncture. We summarized the characteristics of current clinical studies, including the types of participants, study designs, and clinical outcomes. The published findings from basic neuroimaging studies support the hypothesis that acupuncture alters abnormal neuroplasticity and brain activity. The benefits of acupuncture require further investigation through basic and clinical studies.

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“… 4 , 7 , 8 Anti‐inflammatory therapies thus represent a promising approach to preventing or treating HS development. 9 , 10 , 11 , 12 …”

Section: Introductionmentioning

confidence: 99%

TSG‐6 inhibits hypertrophic scar fibroblast proliferation by regulating IRE1α/TRAF2/NF‐κB signalling

Liu

et al. 2022

International Wound Journal

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TNF‐stimulated gene (TSG‐6) was reported to suppress hypertrophic scar (HS) formation in a rabbit ear model, and the overexpression of TSG‐6 in human HS fibroblasts (HSFs) was found to induce their apoptotic death. The molecular basis for these findings, however, remains to be clarified. HSFs were subjected to TSG‐6 treatment. Treatment with TSG‐6 significantly suppressed HSF proliferation and induced them to undergo apoptosis. Moreover, TSG‐6 exposure led to reductions in collagen I, collagen III, and α‐SMA mRNA and protein levels, with a corresponding drop in proliferating cell nuclear antigen (PCNA) expression indicative of impaired proliferative activity. Endoplasmic reticulum (ER) stress was also suppressed in these HSFs as demonstrated by decreases in Bip and p‐IRE1α expression, downstream inositol requiring enzyme 1 alpha (IRE1α) ‐Tumor necrosis factor receptor associated factor 2 (TRAF2) pathway signalling was inhibited and treated cells failed to induce NF‐κB, TNF‐α, IL‐1β, and IL‐6 expression. Overall, ER stress was found to trigger inflammatory activity in HSFs via the IRE1α‐TRAF2 axis, as confirmed with the specific inhibitor of IRE1α STF083010. Additionally, the effects of TSG‐6 on apoptosis, collagen I, collagen III, α‐SMA, and PCNA of HSFs were reversed by the IRE1α activator thapsigargin (TG). These data suggest that TSG‐6 administration can effectively suppress the proliferation of HSFs in part via the inhibition of IRE1α‐mediated ER stress‐induced inflammation (IRE1α/TRAF2/NF‐κB signalling).

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Calcitonin gene-related peptide alleviates hypertrophic scar formation by inhibiting the inflammation

Cited by 8 publications

References 27 publications

Dural Immune Cells, CGRP, and Migraine

Dural Immune Cells, CGRP, and Migraine

Therapeutic applications and potential mechanisms of acupuncture in migraine: A literature review and perspectives

TSG‐6 inhibits hypertrophic scar fibroblast proliferation by regulating IRE1α/TRAF2/NF‐κB signalling

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