Glucagon-like peptide-1 analogue liraglutide facilitates wound healing by activating PI3K/Akt pathway in keratinocytes

Autor: Hiroshi Uchi, Saori Morino-Koga, Masutaka Furue, Mari Oda, Konosuke Nagae, Yuka Tanaka
Rok vydání: 2018
Předmět:
Zdroj: Diabetes research and clinical practice. 146
ISSN: 1872-8227
Popis: Aims Diabetes induces various skin troubles including foot ulcer. This type of skin ulcer is refractory but the pathogenesis is not so certain. Recent study show that glucagon-like peptide-1 (GLP-1) analogues reduce foot complications with diabetes (Perez et al., 2015), however, the role of GLP-1/GLP-1R axis is not fully understood, and clear evidence of GLP-1 to facilitate wound closure is still lacking. In this study, we investigated whether a potent GLP-1R agonist liraglutide affects wound healing process. Methods The expression of GLP-1R in HaCaT cells were indentified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunoblotting analysis. To assess the effect on wound closure in keratinocytes, we performed in vitro scratch assay using the IncuCyte system (Essen BioSciences, Ann Arborm MI). We applied ointment containing liraglutide on full-thickness wounds in the dorsum of female balb/c mice (n = 6) until healing. To investigate the effect on PI3K/Akt pathway, we used IncuCyte system in HaCaT treated with PI3K inhibitor and Akt inhibitor. Results Keratinocytes expressed GLP-1R and liraglutide induced their migration. Liraglutide facilitated the wound healing in mice. Liraglutide upregulated keratinocyte migration via PI3K/Akt activation. Conclusions Our study suggests that liraglutide may be a potential target drug to improve skin ulcer with diabetes through its specific receptor GLP-1.
Databáze: OpenAIRE
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