20(S)-Protopanaxadiol enhances angiogenesis via HIF-1α-mediated VEGF secretion by activating p70S6 kinase and benefits wound healing in genetically diabetic mice

Autor: Xiaojun Wu, Li Yang, Gao Bo, Zhengtao Wang, Eryun Zhang, Huang Lingfang, Hailian Shi
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Vascular Endothelial Growth Factor A
Sapogenins
Angiogenesis
Cell Survival
MAP Kinase Signaling System
Clinical Biochemistry
Neovascularization
Physiologic
Mice
Transgenic
Pharmacology
Biochemistry
Diabetes Mellitus
Experimental
Neovascularization
03 medical and health sciences
chemistry.chemical_compound
Mice
Phosphatidylinositol 3-Kinases
Human Umbilical Vein Endothelial Cells
Medicine
Animals
Humans
RNA
Small Interfering
Molecular Biology
Protein kinase B
PI3K/AKT/mTOR pathway
Ginseng Compound
Tube formation
Wound Healing
business.industry
TOR Serine-Threonine Kinases
Ribosomal Protein S6 Kinases
70-kDa
Hypoxia-Inducible Factor 1
alpha Subunit
Proto-Oncogene Proteins c-raf
030104 developmental biology
chemistry
Immunology
Molecular Medicine
Protopanaxadiol
Original Article
Female
medicine.symptom
business
Wound healing
Proto-Oncogene Proteins c-akt
Signal Transduction
Zdroj: Experimental & Molecular Medicine
ISSN: 2092-6413
1226-3613
Popis: 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. A compound isolated from a type of ginseng plant may have potential for promoting the healing of foot ulcers in people with diabetes. Panax ginseng is widely used in East Asia for its many reputed health benefits. Xiao-jun Wu and colleagues at Shanghai University of Traditional Chinese Medicine tested the ginseng compound protopanaxadiol in mice that had been genetically modified to act as a model for diabetes. Protopanaxadiol enhanced wound healing by promoting the formation of new blood vessels in the process known as angiogenesis. The researchers also uncovered significant details of the molecular signaling pathways that mediate the compound's effect. Diabetic foot ulcers are the most common complication of diabetes and current treatments have only a 50% success rate, often bringing only temporary improvement. The clinical potential of protopanaxadiol warrants further investigation.
Databáze: OpenAIRE
Externí odkaz: