Roles of calcitonin gene-related peptide in facilitation of wound healing and angiogenesis.
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.
Toda
Masaya
M
Department of Pharmacology, Kitasato University School of Medicine, Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
Suzuki
Tatsunori
T
Hosono
Kanako
K
Kurihara
Yukiko
Y
Kurihara
Hiroki
H
Hayashi
Izumi
I
Kitasato
Hedero
H
Hoka
Sumio
S
Majima
Masataka
M
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin