Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep43935
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Funding
- National Natural Science Foundation of China [81372202, 31301119]
- Natural Science Foundation of Chongqing [cstc2014jcyjA10058]
- Specialized Research Fund for the Doctoral Program of Higher Education of China [20130191120035]
- Fundamental Research Funds for the Central Universities [106112016CDJZR235516]
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Therapeutic angiogenesis has been considered as a potential strategy for treating peripheral artery diseases including hind-limb ischemia (HLI); however, no effective drug-based treatment is currently available. Here we showed that intramuscular administration of salidroside, an active compound of Chinese herb Rhodiola, could robustly enhance blood perfusion recovery by promoting neovascularization in HLI mice. We revealed that salidroside promoted skeletal muscle cell migration and paracrine function through inhibiting the transcriptional level of prolyl-hydroxylase domain 3 (PHD3) without affecting PHD1 and PHD2. Paracrine signals from salidroside-treated skeletal muscle cells enhanced endothelial and smooth muscle cells migration, while inhibition of FGF2/FGF2R and PDGF-BB/PDGFR-beta pathways abolished this effect, as well as neovascularization in HLI mice. Furthermore, we elucidated that salidroside inhibition on PHD3 might occur through estrogen receptor alpha (ER alpha). Together, our findings highlights the potential application of salidroside as a novel pharmalogical inhibitor of ER alpha/PHD3 axis for therapeutic angiogenesis in HLI diseases.
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