Interaction of specifically chemically modified dextrans with transforming growth factor β1: potentiation of its biological activity

Fucoidan Modulates the Effect of Transforming Growth Factor (TGF)-.BETA.1 on Fibroblast Proliferation and Wound Repopulation in in Vitro Models of Dermal Wound Repair

“…The binding of TGF-b 1 to heparin (or similar molecules) has been shown to potentiate the biological effects of TGF-b 1 by maintaining it in an active form. 38) whereas another study has shown that a heparin mimic can inhibit the fibrotic effects of TGF-b 1 . 39) Interpretation of our data is further complicated by work of Schmidt et al 40) which showed that a heparin-like molecule can induce increased expression of TGF-b in coronary smooth muscle cells which was associated with the expected inhibition of cell proliferation.…”

Enhancement of the biological activity of BMP‐2 by synthetic dextran derivatives

“…100,000 B groups. Benzylaminated dextran derivatives also bind to FGF-2, 21 TGFb1, 25 VEGF, 22 PDGF-BB, 24 and Cathepsin G, a serine proteinase known to form complexes with heparin. 35 It is also well known that sulfate-containing polysaccharides such as heparin and heparan sulfate bind strongly to several BMPs, including BMP-2, BMP-4, and BMP-7, which possess heparin-binding domains at their N-terminal ends.…”

“…25,29 Briefly, 40 ng BMP-2 was mixed with 100 lg of water-soluble, chemically modified dextrans in running buffer (125 mM sodium acetate, 50 mM Tris-HCL; pH 7) containing 0.5% bovine serum albumin (BSA; Sigma, Saint Quentin Fallavier, France). The BMP-2/dextran complexes were then loaded onto 0.8% agarose gels prepared in running buffer (125 mM sodium acetate, 50 mM Tris-HCL; pH 7); gel electrophoresis was performed at 200 mA for 4 h. Each BMP-2 band was transferred onto a nitrocellulose membrane (Schleicher & Schuell) overnight using a transfer buffer (25 mM Tris-HCL, 192 mM glycine, 20% methanol; pH 9).…”

“…19 Their chemical substitutions involve statistical distribution of chemical groups onto the 1-6 glucosyl units forming the dextran backbone. Appropriate functionalization of this kind confers affinity for growth factors (such as FGF-2, 20,21 VEGF 165 , 22 PDGF-BB, 23,24 and TGFb1 25 ) on the dextran polysaccharides; these biochemical compounds belong to the ''heparin binding growth factor'' (HBGF) family. Such dextran derivatives and their sulfated versions (carboxymethylated, benzylaminated, and sulfated dextrans) have been reported to modulate growth factor (such as FGFs and TGFb1) activity in vitro; although the underlying mechanisms have not yet been entirely elucidated, they have been found to protect these growth factors from proteolytic degradation in a manner similar to the action of HSPG.…”

“…Such dextran derivatives and their sulfated versions (carboxymethylated, benzylaminated, and sulfated dextrans) have been reported to modulate growth factor (such as FGFs and TGFb1) activity in vitro; although the underlying mechanisms have not yet been entirely elucidated, they have been found to protect these growth factors from proteolytic degradation in a manner similar to the action of HSPG. 20,25,26 New procedures for the preparation of functionalized dextrans have since been developed for industrial production. This novel family of dextran derivatives (specifically dextran methylcarboxylate benzylamide or DMCB) differs significantly from previously described compounds due to a change in the benzylamidification process, which allows a more dependable control over the chemical reactions as well as homogeneous and reproducible substitution of dextran chains with regard to molecular weight and substitute distribution.…”