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-beta 1 (TGF-beta 1) and latent TGF-beta 1 (LTGF-beta 1). TGF-beta 1 bound to fucoidan was unable to interact with its reteptor. In agreement with this, fucoidan attenuated the cellular effect of TGF-beta 1 as measured by phosphorylation of Smad2. Binding of fucoidan rendered LTGF-beta 1 resistant to activation as follows. Fucoidan inhibited furin-like proprotein convertase-mediated activation of platelet LTGF-beta 1 without suppression of the enzyme. In addition, acid- or heat-activation of small recombinant LTGF-beta 1 and acid-activation of large LTGF-beta 1 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-beta 1 and LTGF-beta 1. In conclusion, inhibitions of LTGF-beta 1 activation and TGF-beta 1 receptor binding by fucoidan may in part account for its antifibrotic effects. (C) 2013 Elsevier Inc. All rights reserved.