Fucoidan inhibits activation and receptor binding of transforming growth factor-β1.
Fucoidan, a sulfated, fucose-rich polysaccharide isolated from marine brown algae, has antifibrotic effects. We investigated the biologic effects of interactions of fucoidan with transforming growth factor-β1 (TGF-β1) and latent TGF-β1 (LTGF-β1). TGF-β1 bound to fucoidan was unable to interact with its receptor. In agreement with this, fucoidan attenuated the cellular effect of TGF-β1 as measured by phosphorylation of Smad2. Binding of fucoidan rendered LTGF-β1 resistant to activation as follows. Fucoidan inhibited furin-like proprotein convertase-mediated activation of platelet LTGF-β1 without suppression of the enzyme. In addition, acid- or heat-activation of small recombinant LTGF-β1 and acid-activation of large LTGF-β1 in cultured cell supernatant were also inhibited by fucoidan. Fucoidan is a mixture of polysaccharides of different sizes. As molecular weight of fucoidan increases, it had more inhibitory effects on TGF-β1 and LTGF-β1. In conclusion, inhibitions of LTGF-β1 activation and TGF-β1 receptor binding by fucoidan may in part account for its antifibrotic effects.
Division of Nephrology, Department of Internal Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 138-736, Republic of Korea.
Tae Hee
TH
Kim
Eun Kyoung
EK
Lee
Mee Jeong
MJ
Lee
Ji Hyun
JH
Kim
Won Seok
WS
Yang
D000143:Acids; D001792:Blood Platelets / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D006358:Hot Temperature; D006801:Humans; D053779:Latent TGF-beta Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D008970:Molecular Weight; D011134:Polysaccharides / Q000378:metabolism / Q000494:pharmacology*; D043484:Proprotein Convertases / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000143:Acids; D053779:Latent TGF-beta Binding Proteins; D011134:Polysaccharides; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1; C007789:fucoidan; D043484:Proprotein Convertases