Research Papers:

Elevating VEGF-A and PDGF-BB secretion by salidroside enhances neoangiogenesis in diabetic hind-limb ischemia

Agnes Dwi Ariyanti, Julita Sisjayawan, Jing Zhang, Jian-Qi Zhang, Gui-Xue Wang, Makoto Miyagishi, Shou-Rong Wu _ and Vivi Kasim

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Oncotarget. 2017; 8:97187-97205. https://doi.org/10.18632/oncotarget.21907

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Agnes Dwi Ariyanti1,2,*, Julita Sisjayawan1,2,*, Jing Zhang1, Jian-Qi Zhang1, Gui-Xue Wang1,2, Makoto Miyagishi3, Shou-Rong Wu1,2,4 and Vivi Kasim1,2

1The Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China

2State and Local Joint Engineering Laboratory for Vascular Implants, Chongqing 400044, China

3Molecular Composite Medicine Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8566, Japan

4The 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering, Chongqing University, Chongqing 400044, China

*These authors contributed equally to this work

Correspondence to:

Shou-Rong Wu, email: [email protected]

Vivi Kasim, email: [email protected]

Keywords: hind-limb ischemia, diabetes, salidroside, skeletal muscle cells, angiogenesis

Received: June 05, 2017     Accepted: September 23, 2017     Published: October 13, 2017


Hind-limb ischemia (HLI) is one of the major complication of diabetic patients. Angiogenesis potential in diabetic patients is severely disrupted, and the mechanism underlying it has not been fully elucidated, making it an obstacle for developing an efficient therapeutic angiogenesis strategy. Skeletal muscle cells, through their paracrine function, had been known to be critical for neoangiogenesis. Here we found that hyperglycemia upregulates the expression of skeletal muscle cells prolyl hydroxylase domain 3 (PHD3), which resulted in the decrease of the secretion of angiogenic factors, especially VEGF-A and PDGF-BB. We showed that treatment with salidroside, a small molecule drug, significantly suppresses PHD3 expression and increases VEGF-A and PDGF-BB secretion from skeletal muscle cells, which in turn enhances the proliferation and migration potentials of endothelial and smooth muscle cells. Finally, we demonstrated that intramuscular injection of salidroside into the ischemic hind limbs of diabetic HLI model mice could efficiently induce neoangiogenesis and blood perfusion recovery. Thus, our novel findings not only reveal the effects of hyperglycemia on the angiogenesis potential of skeletal muscle cells and the mechanism underlying it, but also provides a novel finding suggesting that salidroside might be a potential small molecule drug for diabetic HLI.

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