کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8537976 | 1561106 | 2018 | 37 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Novel formononetin-7-sal ester ameliorates pulmonary fibrosis via MEF2c signaling pathway
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موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
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چکیده انگلیسی
Pulmonary fibrosis is a progressive disorder with poor prognosis and limited treatment options. Therefore, novel therapeutic drugs should be developed in preclinical studies. In this study, we designed and synthesized a novel compound named formononetin-7-sal ester (FS). We also investigated its anti-pulmonary fibrosis ability on transforming growth factor beta 1 (TGF-β1)-stimulated pulmonary epithelial cells and fibroblasts in vitro and on bleomycin (BLM)-induced pulmonary fibrosis in vivo. FS strongly blocked cell proliferation and migration, which were activated by TGF-β1, thereby reducing the expression of lung fibrosis markers, such as vimentin, alpha-smooth muscle actin (α-SMA), Snail, and collagen I and III, and increasing the expression of the epithelial cell marker E-cadherin. FS ameliorated BLM-induced pulmonary fibrosis in mice and decreased histopathologic fibrosis scores and collagen deposition. A low expression of hydroxyproline, vimentin, α-SMA, and Snail and a high expression of E-cadherin were found in FS-treated lungs compared with BLM-instilled lungs. Using the Cignal Finder 45-Pathway Reporter Array, we tested the regulation of FS in pulmonary fibrosis-associated signaling pathways and observed that FS significantly inhibited the myocyte enhancer factor-2c (MEF2c) signaling pathway. Gain- and loss-of-function studies, rescue experiments and promoter activity testing were designed to further confirm this result in vivo and in vitro. Collectively, our results demonstrated that FS prevents pulmonary fibrosis via the MEF2c signaling pathway.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 356, 1 October 2018, Pages 15-24
Journal: Toxicology and Applied Pharmacology - Volume 356, 1 October 2018, Pages 15-24
نویسندگان
Xueying Zhao, Guiwu Qu, Chenguang Song, Rongrong Li, Weili Liu, Changjun Lv, Xiaodong Song, Jinjin Zhang, Minge Li,