Aim: The
pro-fibrogenic cytokine transforming growth
factor-beta 1 (TGF-β1) has attracted much attention for its potential role in
the etiology of idiopathic pulmonary fibrosis (IPF). Here, we demonstrate that MS80, a novel
sulfated oligosaccharide extracted from seaweed, can bind TGF-β1. The aim of the present study was to
determine whether MS80 is capable of combating TGF-β1-mediated pulmonary
fibrotic events both in vitro and in vivo, and to investigate the
possible underlying mechanisms.
Methods: Surface plasmon resonance was used to uncover the binding profiles
between the compound and TGF-β. MTT
assay, flow cytometry, Western blot analysis, BCA
protein assay and SDS-PAGE gelatin zymography were
used to probe the antifibrotic mechanisms of
MS80. The in vivo fibrotic
efficacy was evaluated in a bleomycin instillation-induced rat model.
Results: We report
that MS80, a new kind of sulfated oligosaccharide extracted from seaweed,
inhibits TGF-β1-induced pulmonary fibrosis in vitro and bleomycin-induced pulmonary fibrosis in vivo. Our results indicated that MS80
competitively inhibited heparin/HS-TGF-β1 interaction through its high binding
affinity for TGF-β1. Moreover, MS80
arrested TGF-β1-induced human embryo pulmonary fibroblast (HEPF) cell proliferation,
collagen deposition and matrix metalloproteinase (MMP) activity. Intriguingly, MS80 deactivated both the
ERK and p38 signaling pathways. MS80 was also a potent suppressor of bleomycin-induced
rat pulmonary fibrosis in vivo, as evidenced by improved pathological
settings and decreased lung collagen contents.
Conclusion: MS
80 in
particular, and perhaps oligosaccharide
in general, offer better pharmacological profiles with appreciably few side
effects and represent a promising class of drug candidates for IPF therapy.
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