Polyporus Polysaccharide Ameliorates Bleomycin-Induced Pulmonary Fibrosis by Suppressing Myofibroblast Differentiation via TGF-β/Smad2/3 Pathway

Polyporus Polysaccharide Ameliorates Bleomycin-Induced Pulmonary Fibrosis by Suppressing Myofibroblast Differentiation via TGF-β/Smad2/3 Pathway
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猪苓多糖通过 TGF-β/Smad2/3 途径抑制肌成纤维细胞分化,改善博来霉素诱导的肺纤维化

DOI:
10.3389/fphar.2020.00767
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发表时间:
2020-05-26
影响因子:
5.6
通讯作者:
Tan, Wenfeng
Tan, Wenfeng
中科院分区:
医学2区
文献类型:
--
作者:
Jiang, Jintao;Wang, Fang;Tan, Wenfeng

文献摘要

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肺纤维化是系统性硬化症(SSc)发病和死亡的主要原因,没有有效的药物治疗。多孔菌多糖(Polyporus polysaccharide,PPS)是从中草药中提取的一种多糖,具有免疫调节、抗肿瘤、抗氧化、降血脂等作用.本研究旨在探讨PPS的抗肝纤维化作用。我们发现PPS显著改善博莱霉素诱导的小鼠肺纤维化。肌成纤维细胞是纤维化疾病中细胞外基质(ECM)蛋白过度沉积的效应细胞。体外研究表明,PPS通过抑制成纤维细胞向肌成纤维细胞转化、抑制ECM沉积、抑制肺成纤维细胞增殖和迁移,发挥有效的抗纤维化作用。我们还发现PPS抑制TGF-β 1诱导的Smad 2/3活化。这项研究是第一个证明PPS在肺中的抗纤维化作用,从而避免了进一步的治疗评价。
Pulmonary fibrosis is a major cause of morbidity and mortality in systemic sclerosis (SSc) with no effective medication. Polyporus polysaccharide (PPS), extracted from Chinese herbs, has immune regulation, anticancer, antioxidant and antiinflammatory activities. This study aims to investigate antifibrotic effects of PPS. We show that PPS markedly ameliorates bleomycin-induced lung fibrosis in mice. Myofibroblasts are the effector cells responsible for excessive deposition of extracellular matrix (ECM) proteins in fibrotic diseases. In vitro evidence reveals that PPS exerts potent antifibrotic effects by inhibiting fibroblast-to-myofibroblast transition, suppressing ECM deposition, and repressing lung fibroblast proliferation and migration. We also find that PPS inhibits TGF-beta 1-induced Smad2/3 activating. This study is the first to demonstrate an antifibrotic role of PPS in lungs, thus warranting further therapeutic evaluation.