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Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis.

Haddad O, Guyot E, Marinval N, Chevalier F, Maillard L, Gadi L, Laguillier-Morizot C, Oudar O, Sutton A, Charnaux N, Hlawaty H - Mar Drugs (2015)

Bottom Line: The phenotypic tests of LMWF-treated and EXT2- or HPSE-siRNA-transfected cells indicated that EXT2 or HPSE expression significantly affect the proangiogenic potential of LMWF.In addition, LMWF increased SDC-1, but decreased SDC-4 expressions.The effect of LMWF depends on SDC-4 expression.

View Article: PubMed Central - PubMed

Affiliation: Inserm U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, Groupe Biothérapies et Glycoconjugués, 93000 Bobigny, France. haddad.oualid@univ-paris13.fr.

ABSTRACT
Induction of angiogenesis is a potential treatment for chronic ischemia. Low molecular weight fucoidan (LMWF), the sulfated polysaccharide from brown seaweeds, has been shown to promote revascularization in a rat limb ischemia, increasing angiogenesis in vivo. We investigated the potential role of two heparan sulfate (HS) metabolism enzymes, exostosin-2 (EXT2) and heparanase (HPSE), and of two HS-membrane proteoglycans, syndecan-1 and -4 (SDC-1 and SDC-4), in LMWF induced angiogenesis. Our results showed that LMWF increases human vascular endothelial cell (HUVEC) migration and angiogenesis in vitro. We report that the expression and activity of the HS-degrading HPSE was increased after LMWF treatment. The phenotypic tests of LMWF-treated and EXT2- or HPSE-siRNA-transfected cells indicated that EXT2 or HPSE expression significantly affect the proangiogenic potential of LMWF. In addition, LMWF increased SDC-1, but decreased SDC-4 expressions. The effect of LMWF depends on SDC-4 expression. Silencing EXT2 or HPSE leads to an increased expression of SDC-4, providing the evidence that EXT2 and HPSE regulate the SDC-4 expression. Altogether, these data indicate that EXT2, HPSE, and SDC-4 are involved in the proangiogenic effects of LMWF, suggesting that the HS metabolism changes linked to LMWF-induced angiogenesis offer the opportunity for new therapeutic strategies of ischemic diseases.

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Assessment of SDC involvement in biological effects of LMWF in HUVECs. 2D-angiogenesis (A) and migration (B) assays were performed in SDC-1-siRNA- or SDC-4-siRNA- or SNC-siRNA-transfected control cells (B, left panel), or in cells treated with specific anti-SDC-1 or anti-SDC-4 antibodies (B, right panel). Control LMWF induction was arbitrary set at 100% for SNC-siRNA-transfected cells or isotypes. (C) SDC-1 and SDC-4 mRNA expression was analyzed in EXT2- or HPSE-siRNA-transfected cells. * p < 0.05 versus SNC-siRNA-transfected control cells or isotypes. A.U.: arbitrary unit.
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marinedrugs-13-06588-f008: Assessment of SDC involvement in biological effects of LMWF in HUVECs. 2D-angiogenesis (A) and migration (B) assays were performed in SDC-1-siRNA- or SDC-4-siRNA- or SNC-siRNA-transfected control cells (B, left panel), or in cells treated with specific anti-SDC-1 or anti-SDC-4 antibodies (B, right panel). Control LMWF induction was arbitrary set at 100% for SNC-siRNA-transfected cells or isotypes. (C) SDC-1 and SDC-4 mRNA expression was analyzed in EXT2- or HPSE-siRNA-transfected cells. * p < 0.05 versus SNC-siRNA-transfected control cells or isotypes. A.U.: arbitrary unit.

Mentions: Under basal conditions, the 2D-angiogenenis assays showed a significant decrease in cell capillary network length by 23% ± 4% in SDC-1- and by 54% ± 7% in SDC-4-siRNA-transfected cells, as compared to SNC-siRNA-transfected control cells (Figure S3A). Upon LMWF cell treatment, the LMWF-induction of 2D-angiogenenis was unchanged in SDC-1-siRNA-transfected cells, whereas it was significantly increased in SDC-4-siRNA-transfected cells by 62% ± 5% (p < 0.005), as compared to SNC-siRNA-transfected control cells (Figure 8A).


Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis.

Haddad O, Guyot E, Marinval N, Chevalier F, Maillard L, Gadi L, Laguillier-Morizot C, Oudar O, Sutton A, Charnaux N, Hlawaty H - Mar Drugs (2015)

Assessment of SDC involvement in biological effects of LMWF in HUVECs. 2D-angiogenesis (A) and migration (B) assays were performed in SDC-1-siRNA- or SDC-4-siRNA- or SNC-siRNA-transfected control cells (B, left panel), or in cells treated with specific anti-SDC-1 or anti-SDC-4 antibodies (B, right panel). Control LMWF induction was arbitrary set at 100% for SNC-siRNA-transfected cells or isotypes. (C) SDC-1 and SDC-4 mRNA expression was analyzed in EXT2- or HPSE-siRNA-transfected cells. * p < 0.05 versus SNC-siRNA-transfected control cells or isotypes. A.U.: arbitrary unit.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663543&req=5

marinedrugs-13-06588-f008: Assessment of SDC involvement in biological effects of LMWF in HUVECs. 2D-angiogenesis (A) and migration (B) assays were performed in SDC-1-siRNA- or SDC-4-siRNA- or SNC-siRNA-transfected control cells (B, left panel), or in cells treated with specific anti-SDC-1 or anti-SDC-4 antibodies (B, right panel). Control LMWF induction was arbitrary set at 100% for SNC-siRNA-transfected cells or isotypes. (C) SDC-1 and SDC-4 mRNA expression was analyzed in EXT2- or HPSE-siRNA-transfected cells. * p < 0.05 versus SNC-siRNA-transfected control cells or isotypes. A.U.: arbitrary unit.
Mentions: Under basal conditions, the 2D-angiogenenis assays showed a significant decrease in cell capillary network length by 23% ± 4% in SDC-1- and by 54% ± 7% in SDC-4-siRNA-transfected cells, as compared to SNC-siRNA-transfected control cells (Figure S3A). Upon LMWF cell treatment, the LMWF-induction of 2D-angiogenenis was unchanged in SDC-1-siRNA-transfected cells, whereas it was significantly increased in SDC-4-siRNA-transfected cells by 62% ± 5% (p < 0.005), as compared to SNC-siRNA-transfected control cells (Figure 8A).

Bottom Line: The phenotypic tests of LMWF-treated and EXT2- or HPSE-siRNA-transfected cells indicated that EXT2 or HPSE expression significantly affect the proangiogenic potential of LMWF.In addition, LMWF increased SDC-1, but decreased SDC-4 expressions.The effect of LMWF depends on SDC-4 expression.

View Article: PubMed Central - PubMed

Affiliation: Inserm U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, Groupe Biothérapies et Glycoconjugués, 93000 Bobigny, France. haddad.oualid@univ-paris13.fr.

ABSTRACT
Induction of angiogenesis is a potential treatment for chronic ischemia. Low molecular weight fucoidan (LMWF), the sulfated polysaccharide from brown seaweeds, has been shown to promote revascularization in a rat limb ischemia, increasing angiogenesis in vivo. We investigated the potential role of two heparan sulfate (HS) metabolism enzymes, exostosin-2 (EXT2) and heparanase (HPSE), and of two HS-membrane proteoglycans, syndecan-1 and -4 (SDC-1 and SDC-4), in LMWF induced angiogenesis. Our results showed that LMWF increases human vascular endothelial cell (HUVEC) migration and angiogenesis in vitro. We report that the expression and activity of the HS-degrading HPSE was increased after LMWF treatment. The phenotypic tests of LMWF-treated and EXT2- or HPSE-siRNA-transfected cells indicated that EXT2 or HPSE expression significantly affect the proangiogenic potential of LMWF. In addition, LMWF increased SDC-1, but decreased SDC-4 expressions. The effect of LMWF depends on SDC-4 expression. Silencing EXT2 or HPSE leads to an increased expression of SDC-4, providing the evidence that EXT2 and HPSE regulate the SDC-4 expression. Altogether, these data indicate that EXT2, HPSE, and SDC-4 are involved in the proangiogenic effects of LMWF, suggesting that the HS metabolism changes linked to LMWF-induced angiogenesis offer the opportunity for new therapeutic strategies of ischemic diseases.

Show MeSH
Related in: MedlinePlus