The S1PR1 agonist SEW2871 promotes the survival of skin flap

Can J Physiol Pharmacol. 2021 Dec;99(12):1280-1287. doi: 10.1139/cjpp-2021-0006. Epub 2021 Jul 26.

Abstract

Skin flap transfer is an important method to repair and reconstruct various tissue defects; however, avascular necrosis largely affects the success of flap transfer. The sphingosine 1-phosphate receptor 1 (S1PR1) agonist SEW2871 has been proven to ameliorate ischemic injury; however, its effect on flap survival has not been reported. In this study, an experimental skin flap model was established in rats to investigate the roles of SEW2871. The results indicated that SEW2871 greatly increased the survival of the skin flap, alleviated pathological injury, promoted the angiogenesis, and inhibited cells apoptosis in skin flap tissues. SEW2871 activated S1PR1 downstream signaling pathways, including heat shock protein 27 (HSP27), extracellular regulated protein kinases (ERK), and protein kinase B (Akt). In addition, SEW2871 promoted the expression of S1PR1. These findings may provide novel insights for skin flap transfer.

Keywords: angiogenesis; angiogenèse; apoptose; apoptosis; lambeau cutané; skin flap; sphingosine 1-phosphate.

MeSH terms

  • Angiogenesis Inducing Agents
  • Animals
  • Apoptosis / drug effects
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Gene Expression / drug effects
  • Graft Survival / drug effects*
  • Graft Survival / genetics*
  • HSP27 Heat-Shock Proteins / metabolism
  • Oxadiazoles / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Skin / blood supply*
  • Skin / pathology
  • Skin Transplantation / methods*
  • Sphingosine-1-Phosphate Receptors / genetics
  • Sphingosine-1-Phosphate Receptors / metabolism
  • Sphingosine-1-Phosphate Receptors / physiology*
  • Surgical Flaps / blood supply
  • Surgical Flaps / transplantation*
  • Thiophenes / pharmacology*

Substances

  • Angiogenesis Inducing Agents
  • HSP27 Heat-Shock Proteins
  • Oxadiazoles
  • S1PR1 protein, rat
  • SEW2871
  • Sphingosine-1-Phosphate Receptors
  • Thiophenes
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases