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MS80, a novel sulfated oligosaccharide, inhibits pulmonary fibrosis by targeting TGF-β1 both in vitro and in vivo

   
@article{APS5107,
	author = {Han-dong Jiang and Hua-shi Guan},
	title = {MS80, a novel sulfated oligosaccharide, inhibits pulmonary fibrosis by targeting TGF-β1 both in vitro and in vivo},
	journal = {Acta Pharmacologica Sinica},
	volume = {30},
	number = {7},
	year = {2016},
	keywords = {},
	abstract = {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: MS80 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.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/5107}
}