Low-molecular-weight fucoidan attenuates bleomycin-induced pulmonary fibrosis: possible role in inhibiting TGF-β1-induced epithelial-mesenchymal transition through ERK pathway

American Journal of Translational Research

Chen Wang¹  Lu Wang²  Qingyuan Zhan³  Yi Zhang⁴  Pan Zhang⁵  Xinpeng Li⁶ 

[1] Peking Union Medical Collage, Beijing 100021, P. R. China;Beijing University of Chinese Medicine, Beijing 100029, P. R. China;Chinese Academy of Medical Sciences;College of Pharmacy, LinYi University, Linyi 276000, P. R. China;Department of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, China-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Beijing 100029, P. R. China;The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou 310006, P. R. China

关键词: Low-molecular-weight fucoidan;    pulmonary fibrosis;    epithelial-mesenchymal transition;    TGF-β;    1/ERK;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

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.

【 授权许可】

CC BY-NC