2. Academic Validation
  3. Sulfated polysaccharide JCS1S2 inhibits angiogenesis via targeting VEGFR2/VEGF and blocking VEGFR2/Erk/VEGF signaling

Sulfated polysaccharide JCS1S2 inhibits angiogenesis via targeting VEGFR2/VEGF and blocking VEGFR2/Erk/VEGF signaling

  • Carbohydr Polym. 2019 Mar 1;207:502-509. doi: 10.1016/j.carbpol.2018.11.091.
Zheng Wang 1,  Can Jin 2,  Xueying Li 3,  Kan Ding 4
Affiliations

Affiliations

  • 1 University of Science and Technology of China, No.96, Jinzhai Road Baohe District, Hefei, Anhui, 230026, PR China; Glycochemistry and Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, PR China; University of Chinese Academy of Sciences, No.19A, Yuquan Road, Beijing 100049, PR China.
  • 2 Glycochemistry and Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, PR China; University of Chinese Academy of Sciences, No.19A, Yuquan Road, Beijing 100049, PR China; School of Pharmacy, Zunyi Medical University, 201 Dalian Road, Zunyi 563003, PR China.
  • 3 Glycochemistry and Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, PR China; University of Chinese Academy of Sciences, No.19A, Yuquan Road, Beijing 100049, PR China.
  • 4 Glycochemistry and Glycobiology Lab, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, PR China; University of Chinese Academy of Sciences, No.19A, Yuquan Road, Beijing 100049, PR China. Electronic address: dingkan@simm.ac.cn.
PMID: 30600033 DOI: 10.1016/j.carbpol.2018.11.091
Abstract

More and more evidences suggested that sulfated natural glycans had impact on angiogenesis. However, the molecular targets and functional mechanism of glycans are still vague. JCS1S2 was the sulfated mannoglucan featured with a backbone of 1, 4-linked β-Manp and 1, 4-linked α-Glcp with sulfation at C-6 of β-Manp and α-Glcp residues, respectively. The degree of substitution of this sulfated polysaccharide was 1.74 and its molecular weight was 56.2 kDa. We provided evidences that JCS1S2 could disrupt angiogenesis both in vitro and in vivo. This sulfated polysaccharide inhibited migration and tube formation of human microvascular endothelial cells (HMEC-1) whereas showed no effect on the cells proliferation. Further study uncovered that JCS1S2 bound to both VEGF (vascular endothelial growth factor) (KD value: 4.82 × 10-9) and VEGFR2/KDR/Flk-1 (Vascular Endothelial Growth Factor Receptor 2) (KD value: 1.50 × 10-7) to inactivate VEGFR2/KDR/Flk-1 phosphorylation. In addition, JCS1S2 blocked downstream signaling and impaired the expression of VEGF and its transcription factor AP-1 (Activator protein-1). These results demonstrated that JCS1S2 interrupted angiogenesis via blocking VEGF signaling transduction and could be a potential anti-angiogenetic agent for disease treatment.

Keywords

Angiogenesis; Dendrobium nobile Lindl; HMEC-1; Sulfated polysaccharide; VEGF.

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