Roles of calcitonin gene-related peptide in facilitation of wound healing and angiogenesis
Roles of calcitonin gene-related peptide in facilitation of wound healing and angiogenesis
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DOI：
10.1016/j.biopha.2008.02.003
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发表时间：
2008-07-01
影响因子：
7.5
通讯作者：
Majima, Masataka
中科院分区：
文献类型：
--
作者：
Toda, Masaya;Suzuki, Tatsunori;Majima, Masataka
降钙素基因相关肽(CGRP)是降钙素/CGRP基因初级转录产物的组织特异性选择性剪接产物，由37个氨基酸组成。降钙素基因相关肽广泛分布于中枢和外周神经系统，在哺乳动物体内具有广泛的生物活性。在目前的研究中，我们检查了神经系统释放的内源性CGRP是否促进了伤口愈合所必需的新生血管形成。在CGRP基因敲除小鼠(CGRP-/-)中，创伤诱导的血管生成和伤口闭合与野生型小鼠相比明显受到抑制。CGRP-/-的愈合受抑伴随着创面肉芽组织中血管内皮生长因子(VEGF)表达的减少。CGRP拮抗剂CGRP8-37皮下注射微渗泵后，可阻断创面愈合过程，减少创面肉芽组织中CD31和VEGF的表达。与赋形剂处理的小鼠相比，用辣椒素预处理的神经肽耗竭小鼠的伤口愈合过程显著延迟。这些结果表明，神经系统来源的CGRP可能促进伤口愈合和血管生成。靶向CGRP可能在控制与病理生理条件相关的血管生成方面有希望。(C)2008年，爱思唯尔·马森公司出版。
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 miniosmotic 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. (c) 2008 Published by Elsevier Masson SAS.