Malinda Katherine M, Wysocki Annette B, Koblinski Jennifer E, Kleinman Hynda K, Ponce M Lourdes
Review Branch DERA, NHLBI, NIH, Bethesda, MD 20892-1857, USA.
Int J Biochem Cell Biol. 2008;40(12):2771-80. doi: 10.1016/j.biocel.2008.05.025. Epub 2008 Jun 20.
Acceleration of the wound healing process by using angiogenic peptides has been demonstrated previously. Here we used select laminin-111 peptides, A13 and C16, from the laminin alpha1 and gamma1 chain, respectively, to test whether they are able to stimulate wound healing in a rat full thickness wound model. The 12-mer peptides C16 and A13 are highly angiogenic and bind to integrins alphavbeta3 and alpha5beta1. We show that A13 increases wound re-epithelialization as much as 17% over controls by day 4 and C16 increases coverage by 11%. Contraction of the treated wounds was increased as much as 11% for A13 and 8% for C16 at day 4. No differences were observed at day 7 with either peptide. The peptides also stimulated fibroblast migration in Boyden chamber assays. A13 increased cell migration as much as 2.4-fold on uncoated filters and as much as 16-fold on collagen type IV-coated filters over negative controls. Similarly, C16 also stimulated migration 1.8-fold on uncoated filters and as much as 12-fold on collagen-coated filters. A13 and C16 significantly decreased expression of the pro and active forms of matrix metalloproteinase 2 in foreskin fibroblasts indicating their role in collagen accumulation. We conclude that small bioactive angiogenic peptides can promote dermal wound healing and may offer a new class of stable and chemically manipulable therapeutics for wound healing.
先前已证明使用血管生成肽可加速伤口愈合过程。在此,我们分别使用了来自层粘连蛋白α1链和γ1链的选定层粘连蛋白-111肽A13和C16,以测试它们是否能够在大鼠全层伤口模型中刺激伤口愈合。12肽C16和A13具有高度血管生成性,并与整合素αvβ3和α5β1结合。我们发现,到第4天时,A13使伤口再上皮化程度比对照组提高了17%,C16使覆盖面积增加了11%。在第4天时,A13处理的伤口收缩增加了11%,C16增加了8%。在第7天时,两种肽均未观察到差异。这些肽在Boyden小室试验中也刺激了成纤维细胞迁移。与阴性对照相比,A13在未包被的滤膜上使细胞迁移增加了2.4倍,在IV型胶原包被的滤膜上增加了16倍。同样,C16在未包被的滤膜上也刺激迁移1.8倍,在胶原包被的滤膜上增加了12倍。A13和C16显著降低了包皮成纤维细胞中基质金属蛋白酶2的前体和活性形式的表达,表明它们在胶原蛋白积累中的作用。我们得出结论,小的生物活性血管生成肽可以促进皮肤伤口愈合,并可能为伤口愈合提供一类新的稳定且可化学操控的治疗方法。