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

Konosuke Nagae, Hiroshi Uchi, Saori Morino-Koga, Yuka Tanaka, Mari Oda, Masutaka Furue

研究成果: ジャーナルへの寄稿記事

1 引用 (Scopus)

抄録

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 (Pérez 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.

元の言語英語
ページ(範囲)155-161
ページ数7
ジャーナルDiabetes Research and Clinical Practice
146
DOI
出版物ステータス出版済み - 12 2018

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Glucagon-Like Peptide 1
Phosphatidylinositol 3-Kinases
Keratinocytes
Wound Healing
Skin Ulcer
Wounds and Injuries
Foot Ulcer
Diabetes Complications
Ointments
Immunoblotting
Reverse Transcription
Liraglutide
Foot
Polymerase Chain Reaction
Skin
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

これを引用

Glucagon-like peptide-1 analogue liraglutide facilitates wound healing by activating PI3K/Akt pathway in keratinocytes. / Nagae, Konosuke; Uchi, Hiroshi; Morino-Koga, Saori; Tanaka, Yuka; Oda, Mari; Furue, Masutaka.

:: Diabetes Research and Clinical Practice, 巻 146, 12.2018, p. 155-161.

研究成果: ジャーナルへの寄稿記事

Nagae, Konosuke ; Uchi, Hiroshi ; Morino-Koga, Saori ; Tanaka, Yuka ; Oda, Mari ; Furue, Masutaka. / Glucagon-like peptide-1 analogue liraglutide facilitates wound healing by activating PI3K/Akt pathway in keratinocytes. :: Diabetes Research and Clinical Practice. 2018 ; 巻 146. pp. 155-161.
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abstract = "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 (P{\'e}rez 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.",
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AU - Morino-Koga, Saori

AU - Tanaka, Yuka

AU - Oda, Mari

AU - Furue, Masutaka

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N2 - 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 (Pérez 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.

AB - 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 (Pérez 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.

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