Roles of calcitonin gene-related peptide in facilitation of wound healing and angiogenesis
Abstract
Calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide produced by tissue-specific alternative splicing of the primary transcript of the calcitonin/CGRP gene. CGRP is widely distributed in the central and peripheral neuronal systems and exhibits numerous biological activities in mammals. We examined in the present study whether or not endogenous CGRP released from neuronal systems facilitates neovascularization indispensable to wound healing. In CGRP knockout mice (CGRP-/-), wound-induced angiogenesis and wound closure were significantly suppressed compared with those in wild-type mice. The suppressed healing in CGRP-/- was accompanied by reduction in expressions of vascular endothelial growth factor (VEGF) in the wound granulation tissues. A CGRP antagonist, CGRP8-37 when infused with mini-osmotic pumps subcutaneously blocked the wound healing processes and reduced the expressions of CD31 and VEGF expression in the wound granulation tissues. Wound healing process was significantly delayed in neuropeptide-depleted mice pretreated with capsaicin, compared with vehicle-treated mice. These results indicate that CGRP derived from neuronal systems may facilitate wound healing and angiogenesis. Targeting of CGRP may be promising in controlling angiogenesis related to pathophysiological conditions.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Genetic deletion or blockade of CGRP receptors is detrimental to wound healing.
“Similarly, genetic deletion or blockade of CGRP receptors has been suggested to be detrimental to wound healing58–60.”
From Neuropeptides Substance P and Calcitonin Gene Related Peptide Accelerate the Development and Fibrogenesis of Endometriosis (2019) · cites this paper as [60]
Cites
Mechanisms of angiogenesis and arteriogenesis
Carmeliet, P. (2000) · Nature Medicine · doi:10.1038/74651 · Cited by 4,146 · see citing works
Molecular mechanisms of nociception
Julius, D., & Basbaum, A. I. (2001) · Nature · doi:10.1038/35093019 · Cited by 2,685 · see citing works
Takahashi, T., Kalka, C., Masuda, H., Chen, D., Silver, M., Kearney, M., Magner, M., Isner, J. M., & Asahara, T. (1999) · Nature Medicine · doi:10.1038/7434 · Cited by 2,421 · see citing works
Amara, S. G., Jonas, V., Rosenfeld, M. G., Ong, E. S., & Evans, R. M. (1982) · Nature · doi:10.1038/298240a0 · Cited by 2,105 · see citing works
Common mechanisms of nerve and blood vessel wiring
Carmeliet, P., & Tessier-Lavigne, M. (2005) · Nature · doi:10.1038/nature03875 · Cited by 1,085 · see citing works
Eto, T., & Takahashi, H. (1999) · Nature Medicine · doi:10.1038/8462 · Cited by 914 · see citing works
Retinal angiogenesis in development and disease
Gariano, R. F., & Gardner, T. W. (2005) · Nature · doi:10.1038/nature04482 · Cited by 707 · see citing works
Mukouyama, Y., Shin, D., Britsch, S., Taniguchi, M., & Anderson, D. J. (2002) · Cell · doi:10.1016/s0092-8674(02)00757-2 · Cited by 658 · see citing works
Wimalawansa, S. J. (1996) · Endocrine Reviews · doi:10.1210/edrv-17-5-533 · Cited by 490 · see citing works
Host Prostaglandin E2-EP3 Signaling Regulates Tumor-Associated Angiogenesis and Tumor Growth
Amano, H., Hayashi, I., Endo, H., Kitasato, H., Yamashina, S., Maruyama, T., Kobayashi, M., Satoh, K., Narita, M., Sugimoto, Y., et al. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20021408 · Cited by 325 · see citing works
Self-citationNeural emergency system in the stomach
Holzer, P. D. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70597-9 · Cited by 276 · see citing works
Weidner, C., Klede, M., Rukwied, R., Lischetzki, G., Neisius, U., Schmelz, M., Skov, P. S., & Petersen, L. J. (2000) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2000.00142.x · Cited by 256 · see citing works
Neuropeptides and their receptors: innovative science providing novel therapeutic targets
Brain, S. D., & Cox, H. M. (2006) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0706461 · Cited by 195 · see citing works
Elevated Sympathetic Nervous Activity in Mice Deficient in αCGRP
Oh-hashi, Y., Shindo, T., Kurihara, Y., Imai, T., Wang, Y., Morita, H., Imai, Y., Kayaba, Y., Nishimatsu, H., Suematsu, Y., et al. (2001) · Circulation Research · doi:10.1161/hh2301.100812 · Cited by 154 · see citing works
Self-citationSzolcsányi, J., Helyes, Z., Oroszi, G., et al. (1998) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701685 · Cited by 126 · see citing works
Bodolay, E., Koch, A. E., Kim, J. M., Szegedi, G., & Szekanecz, Z. (2002) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2002.tb00514.x · Cited by 114 · see citing works
Ohno, T., Hattori, Y., Komine, R., Ae, T., Mizuguchi, S., Arai, K., Saeki, T., Suzuki, T., Hosono, K., Hayashi, I., et al. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.10.001 · Cited by 95 · see citing works
Self-citationBenrath, J., Zimmermann, M., & Gillardon, F. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)12062-9 · Cited by 89 · see citing works
Angiogenesis in Rheumatoid Arthritis: Pathogenic and Clinical Significance
Szekanecz, Z., Szegedi, G. Y., & Ae, K. (1998) · Journal of Investigative Medicine · doi:10.1177/108155899804600207 · Cited by 74 · see citing works
Endothelium‐dependent sensory NANC vasodilatation: involvement of ATP, CGRP and a possible NO store
Kakuyama, M., Vallance, P. J., & Ahluwalia, A. (1998) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701610 · Cited by 55 · see citing works
Kamoshita, E., Ikeda, Y., Fujita, M., Amano, H., Oikawa, A., Suzuki, T., Ogawa, Y., Yamashina, S., Azuma, S., Narumiya, S., et al. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.051358 · Cited by 53 · see citing works
Self-citationSaeki, T., Ohno, T., Kamata, K., et al. (2004) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00538.2002 · Cited by 36 · see citing works
Sensory nerves, nitric oxide and NANC vasodilatation.
Holzer, P. D., Wachter, C. H., Heinemann, Á., et al. (1995) · PubMed · Cited by 34 · see citing works
Cadieux, A., MONAST, N. P., Pomerleau, F., et al. (1999) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.159.1.9711031 · Cited by 31 · see citing works
Nerves Tell Arteries to Make Like a Tree
Miller, G. (2002) · Science · doi:10.1126/science.296.5576.2121a · Cited by 23 · see citing works
Hayashi, H., Ohno, T., Nishiyama, K., et al. (2001) · The Japanese Journal of Pharmacology · doi:10.1254/jjp.86.351 · Cited by 21 · see citing works
Mizuguchi, S., OHNO, T., Hattori, Y., et al. (2005) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2004.03764.x · Cited by 20 · see citing works
Les mécanismes de lˈangiogenèse. Applications médicales et thérapeutiques
Couffinhal, T., Dufourcq, P., Daret, D., & Duplàa, C. (2001) · La Revue de Médecine Interne · doi:10.1016/s0248-8663(01)00472-6 · Cited by 20 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Yan, D., Liu, X., & Guo, S.-W. (2019) · Scientific Reports · doi:10.1038/s41598-019-39170-w · Cited by 82 · see citing works
Kurashige, C., Hosono, K., Matsuda, H., Tsujikawa, K., Okamoto, H., & Majima, M. (2014) · The FASEB Journal · doi:10.1096/fj.13-238998 · Cited by 67 · see citing works
Self-citationResearch progress in calcitonin gene-related peptide and bone repair
Wang, Q., Qin, H., Deng, J., Xu, H., Liu, S., Weng, J., & Zeng, H. (2023) · Biomolecules · doi:10.3390/biom13050838 · Cited by 58 · see citing works
- Authors
- Toda, M., Suzuki, T., Hosono, K., Kurihara, Y., Kurihara, H., Hayashi, I., Kitasato, H., Hoka, S., & Majima, M.
- Affiliations
- Kitasato University (JP)
- The University of Tokyo (JP)
- Nihon Pharmaceutical University (JP)
- Corresponding author
- Majima, Masataka
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 62
- Issue
- 6
- Pages
- 352-359
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W1974406387
- Cited by
- 130
- References
- 28
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 17 · 2023: 7 · 2022: 10 · 2021: 7 · 2020: 10 · 2019: 6 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 8 · 2012: 8
- FWCI
- 6.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Kitasato University
- Topics
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- calcitonin gene-related peptide, wound healing, angiogenesis, neovascularization, vascular endothelial growth factor, capsaicin, CGRP8-37, CD31, granulation tissue, neuropeptides
- MeSH terms
- Animals, Capsaicin, Disease Models, Animal, Gene Expression Regulation, Male, Mice, Inbred C57BL, Wound Healing, Calcitonin Gene-Related Peptide, Drug Delivery Systems, Mice, Knockout, Neovascularization, Physiologic, Platelet Endothelial Cell Adhesion Molecule-1, Vascular Endothelial Growth Factor A, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
