The S1PR1 agonist SEW2871 promotes the survival of skin flap

• Published in: Canadian journal of physiology and pharmacology 2021-12, Vol.99 (12), p.1280-1287
• Main Authors: Zhang, Dongdong, Qi, Dongxu, Xu, Yi, Hu, Chunhe, Zhang, Xiao, Yang, Qingjian, Shang, Zikun, Zhang, Guisheng
• Format: Article
• Language: English
• Subjects: Agonists; AKT protein; Angiogenesis; Angiogenesis Inducing Agents; angiogenèse; Animals; apoptose; Apoptosis; Apoptosis - drug effects; Avascular necrosis; Extracellular signal-regulated kinase; Extracellular Signal-Regulated MAP Kinases - metabolism; Flaps (Surgery); Gene Expression - drug effects; Graft Survival - drug effects; Graft Survival - genetics; Health aspects; Heat shock proteins; HSP27 Heat-Shock Proteins - metabolism; Hsp27 protein; Immunosuppressive agents; Ischemia; Kinases; lambeau cutané; Medical research; Medicine, Experimental; Nitric oxide; Oxadiazoles - pharmacology; Physiological aspects; Prevention; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Rats; Rats, Sprague-Dawley; Signal Transduction - drug effects; Signal Transduction - genetics; Skin; Skin - blood supply; Skin - pathology; skin flap; Skin Transplantation - methods; Skin-grafting; Sphingolipids; Sphingosine 1-phosphate; Sphingosine-1-Phosphate Receptors - genetics; Sphingosine-1-Phosphate Receptors - metabolism; Sphingosine-1-Phosphate Receptors - physiology; Surgical Flaps - blood supply; Surgical Flaps - transplantation; Thiophenes - pharmacology
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2021-0006

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.