Dibutyryl cAMP influences endothelial progenitor cell recruitment during wound neovascularization
Dibutyryl cAMP influences endothelial progenitor cell recruitment during wound neovascularization
复制标题
DOI：
10.1038/sj.jid.5700188
复制
发表时间：
2006-05-01
影响因子：
6.5
通讯作者：
Kishimoto, Saburo
中科院分区：
文献类型：
--
作者：
Asai, Jun;Takenaka, Hideya;Kishimoto, Saburo
伤口愈合延迟是糖尿病的主要并发症之一，它是由细胞浸润延迟、血管生成减少、胶原纤维形成和组织减少引起的。最近，从外周血中分离的内皮祖细胞（EPC）被证明在伤口愈合过程中会在新生血管的部位积聚。本研究验证了n -6,2'- o -二丁基腺苷-30,50-环磷酸钠（DBcAMP）的假设，该假设已被证明可以加速伤口愈合，促进EPC进入伤口，并有助于刺激遗传性糖尿病小鼠的新生血管。局部应用DBcAMP可显著加速伤口愈合和伤口血管化，部分原因是通过增强EPC的募集。在dbcamp处理的伤口中，EPC主要局限于肉芽组织边界的细胞团，这是血液供应最不足的部位。DBcAMP处理可提高创面组织、体外培养成纤维细胞和巨噬细胞中血管生成因子、血管内皮生长因子（VEGF）和基质细胞源性因子-1 α (SDF-1 α) mRNA的表达。dbcamp处理的细胞培养上清液增强了EPC迁移。综上所述，这些结果表明DBcAMP促进伤口愈合中的新生血管形成，至少部分是通过增加伤口部位EPC的积累。
Delayed wound healing is one of the major complications of diabetes, and is caused by delayed cellular infiltration, reduced angiogenesis, and decreased formation and organization of collagen fibers. Recently, endothelial progenitor cells (EPC) isolated from peripheral blood were shown to accumulate at sites of neovascularization during wound healing. The present study tested the hypothesis that sodium N-6,2'-O-dibutyryl adenosine-30,50-cyclic phosphate (DBcAMP), which has been shown to accelerate wound healing, promotes recruitment of EPC into wounds and contributes to the stimulation of neovascularization in genetically diabetic mice. Topical application of DBcAMP resulted in significant acceleration of wound healing and wound vascularization partly via enhanced recruitment of EPC. EPC in DBcAMP-treated wounds were mainly localized to cell clusters at the border of the granulation tissue, a site where blood supply is most insufficient. DBcAMP treatment increased the mRNA expression of angiogenic cytokines vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 alpha (SDF-1 alpha) in vivo in wound tissue and in cultured fibroblasts and macrophages, in vitro. Culture supernatants of DBcAMP-treated cells enhanced EPC migration. Taken together, these results indicate that DBcAMP promotes neovascularization in wound healing, at least partly by increasing the accumulation of EPC at wound sites.