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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2017.1
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Impaired angiogenesis is one of the crucial factors that impede the wound healing process in diabetic foot ulcers (DFUs). In this study, we found that 20(S)-protopanaxadiol (PPD), an aglycone of ginsenosides in Panax notoginseng, stimulated angiogenesis and benefited wound healing in genetically diabetic mice. In HUVECs, PPD promoted cell proliferation, tube formation and VEGF secretion accompanied by increased nuclear translocalization of HIF-1α, which led to elevated VEGF mRNA expression.
PPD activated both PI3K/Akt/mTOR and Raf/MEK/ERK signaling pathways in HUVECs, which were abrogated by LY294002 and PD98059. Furthermore, these two pathways had crosstalk through p70S6K, as LY294002, PD98059 and p70S6K siRNA abolished the angiogenic responses of PPD. In the excisional wound splinting model established in db/db diabetic mice, PPD (0.6, 6 and 60 mg ml− 1) accelerated wound closure, which was reflected by a significantly reduced wound area and epithelial gaps, as well as elevated VEGF expression and capillary formation. In addition, PPD activated PI3K/Akt/ERK signaling pathways, as well as enhanced p70S6K activity and HIF-1α synthesis in the wounds. Overall, our results revealed that PPD stimulated angiogenesis via HIF-1α-mediated VEGF expression by activating p70S6K through PI3K/Akt/mTOR and Raf/MEK/ERK signaling cascades, which suggests that the compound has potential use in wound healing therapy in patients suffering from DFUs.
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참고문헌 (23)
참고문헌 신청
Adams RH / 2007 / Molecular regulation of angiogenesis and lymphangiogenesis / Nat Rev Mol Cell Biol 8 : 464 ~ 478
Bader AG / 2005 / Oncogenic PI3K deregulates transcription and translation / Nat Rev Cancer 5 : 921 ~ 929
Boulton AJM / 2005 / The global burden of diabetic foot disease / Lancet 366 : 1719 ~ 1724
Brantley JN / 2015 / Use of placental membranes for the treatment of chronic diabetic foot ulcers / Adv Wound Care 4 : 545 ~ 559
Cho YL / 2015 / Specific activation of insulin-like growth factor-1 receptor by ginsenoside Rg5 promotes angiogenesis and vasorelaxation / J Biol Chem 290 : 467 ~ 477
Bader AG / 2005 / Oncogenic PI3K deregulates transcription and translation / Nat Rev Cancer 5 : 921 ~ 929
Boulton AJM / 2005 / The global burden of diabetic foot disease / Lancet 366 : 1719 ~ 1724
Brantley JN / 2015 / Use of placental membranes for the treatment of chronic diabetic foot ulcers / Adv Wound Care 4 : 545 ~ 559
Cho YL / 2015 / Specific activation of insulin-like growth factor-1 receptor by ginsenoside Rg5 promotes angiogenesis and vasorelaxation / J Biol Chem 290 : 467 ~ 477
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