Low-molecular-weight fucoidan attenuates bleomycin-induced pulmonary fibrosis. - GreenMedInfo Summary
Low-molecular-weight fucoidan attenuates bleomycin-induced pulmonary fibrosis: possible role in inhibiting TGF-β1-induced epithelial-mesenchymal transition through ERK pathway.
Am J Transl Res. 2019 ;11(4):2590-2602. Epub 2019 Apr 15. PMID: 31105865
The therapeutic options for pulmonary fibrosis (PF), a progressive interstitial disease of the lung, are extremely limited. Studies have shown that transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) functions as a central mediating process that contributes to PF. Also, low-molecular-weight fucoidan (LMWF), a sulfated polysaccharide extracted from brown seaweed, has been reported to have antifibrotic characteristics that can help to alleviate kidney fibrosis by inhibiting TGF-β1-mediated EMT. Thus we hypothesized that LMWF might be an attractive candidate for alleviating PF. Eighty C57BL/6 mice and A549 cells were respectively involved in our vivo and vitro experiments. The lung fibrosis was primarily assessed by hematoxylin and eosin (H&E), Masson's trichrome stain, lung wet-to-dry weight ratio and hydroxyproline content. TGF-β1 levels were determined by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence, and the expression of EMT markers and extracellular signal-regulated kinase (ERK) signaling were mainly based on immunostaining, real-time PCR and Western blot. As expected, our vivo models showed that LMWF was associated with improved lung fibrotic histopathology and significantly reduced lung hydroxyproline content. Levels of TGF-β1 expression in bronchoalveolar lavage fluid (BALF) and lung tissue decreased than it had been before treatment. Immunostaining, real-time PCR, and Western blot demonstrated that the lung EMT phenotype was attenuated and ERK signaling downregulated after LMWF administration. The vitro experiments resulted in a similar pharmacologic inhibitory effect of TGF-β1-induced EMT with downregulated ERK signaling. Collectively, our results preliminary suggested that LMWF could attenuate bleomycin-induced PF by inhibiting TGF-β1-induced EMT through ERK signaling.