Body protective compound-157 enhances alkali-burn wound healing in vivo and promotes proliferation, migration, and angiogenesis in vitro

Drug Des Devel Ther. 2015 Apr 30:9:2485-99. doi: 10.2147/DDDT.S82030. eCollection 2015.

Abstract

Chemical burns take up a high proportion of burns admissions and can penetrate deep into tissues. Various reagents have been applied in the treatment of skin chemical burns; however, no optimal reagent for skin chemical burns currently exists. The present study investigated the effect of topical body protective compound (BPC)-157 treatment on skin wound healing, using an alkali burn rat model. Topical treatment with BPC-157 was shown to accelerate wound closure following an alkali burn. Histological examination of skin sections with hematoxylin-eosin and Masson staining showed better granulation tissue formation, reepithelialization, dermal remodeling, and a higher extent of collagen deposition when compared to the model control group on the 18th day postwounding. BPC-157 could promote vascular endothelial growth factor expression in wounded skin tissues. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cell cycle analysis demonstrated that BPC-157 enhanced the proliferation of human umbilical vein endothelial cells (HUVECs). Transwell assay and wound healing assay showed that BPC-157 significantly promoted migration of HUVECs. We also observed that BPC-157 upregulated the expression of VEGF-a and accelerated vascular tube formation in vitro. Moreover, further studies suggested that BPC-157 regulated the phosphorylation level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) as well as its downstream targets, including c-Fos, c-Jun, and Egr-1, which are key molecules involved in cell growth, migration, and angiogenesis. Altogether, our results indicated that BPC-157 treatment may accelerate wound healing in a model of alkali burn-induced skin injury. The therapeutic mechanism may be associated with accelerated granulation tissue formation, reepithelialization, dermal remodeling, and collagen deposition through ERK1/2 signaling pathway.

Keywords: ERK1/2 signaling pathway; human umbilical vein endothelial cells; pentadecapeptide BPC-157; wound healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Alkalies*
  • Animals
  • Burns, Chemical / drug therapy*
  • Burns, Chemical / pathology
  • Cell Cycle / drug effects
  • Cell Movement / drug effects*
  • Cell Proliferation / drug effects*
  • Gene Expression / drug effects
  • Human Umbilical Vein Endothelial Cells / drug effects
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mice
  • Neovascularization, Physiologic / drug effects*
  • Peptide Fragments / therapeutic use*
  • Proteins / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Skin / pathology
  • Wound Healing / drug effects*

Substances

  • Alkalies
  • Peptide Fragments
  • Proteins
  • BPC 157