Angiogenic laminin-derived peptides stimulate wound healing.
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.
Malinda
Katherine M
KM
Review Branch DERA, NHLBI, NIH, Bethesda, MD 20892-1857, USA.
Wysocki
Annette B
AB
Koblinski
Jennifer E
JE
Kleinman
Hynda K
HK
Ponce
M Lourdes
ML
D042501:Angiogenic Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D007797:Laminin / Q000737:chemistry* / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D012867:Skin / Q000166:cytology; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D042501:Angiogenic Proteins; D024141:Collagen Type IV; D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D007797:Laminin; C084098:laminin A; D020778:Matrix Metalloproteinase 2