Roles of calcitonin gene-related peptide in facilitation of wound healing and angiogenesis

Toda, Masaya; Suzuki, Tatsunori; Hosono, Kanako; Kurihara, Yukiko; Kurihara, Hiroki; Hayashi, Izumi; Kitasato, Hedero; Hoka, Sumio; Murakami, Masataka

doi:10.1016/j.biopha.2008.02.003

Cited by 103 publications

(62 citation statements)

References 25 publications

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“…RAMP1-/-mice are reported to be born normally and present no obvious abnormalities in their appearances [54] . RAMP1-/-exhibited higher blood pressure and LPS-induced inflammatory responses of the RAMP1-/-revealed transient 21 higher serum levels of inflammatory cytokines, including MCP-1, IL-12, TNF-α, IFN-γ, and IL-6. These results resemble the phenotypes of CGRP-/-mice.…”

Section: Phenotypes Of Ramp1 and Ramp3 Knockout Micementioning

confidence: 94%

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Regulation of Adrenomedullin and its Family Peptide by RAMP System – Lessons from Genetically Engineered Mice

Shindo¹,

Sakurai²,

Kamiyoshi³

et al. 2013

CPPS

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Adrenomedullin (ADM), originally identified as a vasodilating peptide, is now recognized to be a pleiotropic molecule involved in both the pathogenesis of cardiovascular diseases and circulatory homeostasis.Homozygotes of ADM knockout mice (ADM-/-) were lethal at mid-gestation with abnormalities of vascular development and this finding clarified the angiogenic potency of ADM. Calcitonin gene-related peptide (CGRP), which has a structure and function similar to that of ADM, has been identified as a family peptide of ADM. Unlike ADM-/-, CGRP-/-were apparently normal. Therefore, the study of knockout mice first clarified the distinctly different physiological roles between ADM and CGRP.In contrast, heterozygotes of ADM knockout mice (ADM+/-) were alive but showed blood pressure elevation, reduced neovascularization, and enhanced neointimal formation by arterial injury.Based on these observations, there was hope ADM would have a therapeutic use.However, ADM has a short half-life in the blood stream and its application in chronic disease has limitations. Therefore, we focused on the ADM receptor system. The calcitonin-receptor-like receptor (CLR), which is the ADM receptor, associates with one of the accessory proteins, called receptor activity-modifying proteins (RAMPs). By interacting with RAMP1, CLR exhibits a high affinity for CGRP, whereas by interacting with either RAMP2 or -3, CLR exhibits a high affinity for ADM.We generated RAMP knockout mice and found that vascular phenotypes similar to ADM-/-were reproduced only in RAMP2-/-. This shows that RAMP2 is the key

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Section: Phenotypes Of Ramp1 and Ramp3 Knockout Micementioning

confidence: 94%

“…With respect to the angiogenic potency of CGRP, tumor-associated angiogenesis and wound healing angiogenesis were reported to be reduced in CGRP-/-compared with those in WT mice [20] [21] . However, unlike ADM, CGRP does not contribute to vascular development during embryogenesis.…”

Section: Cgrp Knockout Micementioning

confidence: 99%

Regulation of Adrenomedullin and its Family Peptide by RAMP System – Lessons from Genetically Engineered Mice

Shindo¹,

Sakurai²,

Kamiyoshi³

et al. 2013

CPPS

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“…Neuropeptides mediate their actions by binding to specific receptors found on various cells in the skin, including immune cells, Langerhans cells, EC, mast cells, fibroblasts and keratinocytes [98]. Several neuropeptides are involved in wound healing, including substance P (SP), neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) [99][100][101] (Table 1).…”

Section: Neuropeptides and Wound Healingmentioning

confidence: 99%

“…CGRP is known to induce neurogenic inflammation, inducing pro-inflammatory response in several cell types, and it also induces the formation of new vessels, important during physiological and pathophysiological wound healing [101,164]. CGRP induces inflammatory pathways but also inflammation can induce CGRP release [165,166].…”

Section: Cgrp Contribution To Inflammation and Angiogenesis In Wound mentioning

confidence: 99%

“…CGRP can also stimulate the proliferation of keratinocytes, EC and melanocytes [164,174,175]. In CGRP knockout mice (CGRP-/-), angiogenesis and wound healing were impaired compared with those in wild-type mice, and a decrease in the release of VEGF from the wound granulation tissues was shown [101]. This suggests that the involvement of CGRP in wound healing is mediated through its effect on angiogenesis.…”

Section: Cgrp Contribution To Inflammation and Angiogenesis In Wound mentioning

confidence: 99%

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Inflammatory and Angiogenic Abnormalities in Diabetic Wound Healing: Role of Neuropeptides and Therapeutic Perspectives

Tellechea¹

2012

TOCVJ

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Diabetic foot ulceration (DFU) is one of the most costly and debilitating complications of diabetes and is the leading cause of non-traumatic amputations, affecting 15% of the diabetic population. Impaired wound healing in diabetic patients without large-vessel disease has been attributed to microvascular dysfunction, neuropathy, and abnormal cellular and inflammatory responses. These abnormalities have been examined mainly in animal models although a few studies have been undertaken in diabetic patients. This review provides an overview of the inflammatory and vascular abnormalities in DFU and emphasises the role of angiogenic growth factors, endothelial progenitor cells (EPCs), and neuropeptides as mediators of wound healing and potential therapeutic agents for these chronic, non-healing ulcers.

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Lessons Learned from CGRP Mutant Mice

Sowers

Tye

Russo

2017

Neurobiological Basis of Migraine

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Roles of calcitonin gene-related peptide in facilitation of wound healing and angiogenesis

Cited by 103 publications

References 25 publications

Regulation of Adrenomedullin and its Family Peptide by RAMP System – Lessons from Genetically Engineered Mice

Regulation of Adrenomedullin and its Family Peptide by RAMP System – Lessons from Genetically Engineered Mice

Inflammatory and Angiogenic Abnormalities in Diabetic Wound Healing: Role of Neuropeptides and Therapeutic Perspectives

Lessons Learned from CGRP Mutant Mice

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