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Astragalus polysaccharides attenuate pulmonary fibrosis by inhibiting the epithelial-mesenchymal transition and NF-?B pathway activation.

ABSTRACT: Astragalus polysaccharides (APS), the active ingredients isolated from the plant Astragalus, have been reported to have numerous biological activities, including anti?inflammatory and antitumor activities. However, the effect of APS on pulmonary fibrosis (PF) remains unknown. The present study aimed to evaluate the protective effect of APS against PF and to explore its underlying mechanisms by using in vivo and in vitro models. A mouse in vivo model of bleomycin?induced PF and an in vitro model of transforming growth factor ?1 (TGF??1)?stimulated human lung epithelial A549 cells were established. Histopathologic examination and collagen deposition were investigated by hematoxylin and eosin staining and Masson staining, and by detecting the hydroxyproline content. The expression of related genes was analyzed by western blotting, reverse transcription?quantitative (RT?q) PCR, immunofluorescence and immunohistochemistry. The results from the in vivo mouse model demonstrated that treatment with APS could ameliorate collagen deposition and reduce fibrotic area and hydroxyproline content in the matrix. Furthermore, APS significantly inhibited the epithelial?mesenchymal transition (EMT), as evidenced by an increased level of E?cadherin and a decreased expression of vimentin and alpha smooth muscle actin. Furthermore, APS treatment significantly decreased TGF??1?induced EMT and NF??B pathway activation in vitro. The results from the present study provided new insights on PF regression via the anti?fibrotic effects of APS.

SUBMITTER: Zhang R

PROVIDER: S-EPMC7255476 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Astragalus polysaccharides attenuate pulmonary fibrosis by inhibiting the epithelial-mesenchymal transition and NF-κB pathway activation.

Zhang Rui R Xu Liming L An Xiaoxia X Sui Xinbing X Lin Shuang S

International journal of molecular medicine 20200413 1

Astragalus polysaccharides (APS), the active ingredients isolated from the plant Astragalus, have been reported to have numerous biological activities, including anti‑inflammatory and antitumor activities. However, the effect of APS on pulmonary fibrosis (PF) remains unknown. The present study aimed to evaluate the protective effect of APS against PF and to explore its underlying mechanisms by using in vivo and in vitro models. A mouse in vivo model of bleomycin‑induced PF and an in vitro model ...[more]

PMID: 32319542

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Project description:BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease with no effective treatment. The epithelial-mesenchymal transition (EMT) is a critical stage during the development of fibrosis. To assess the effect of sulforaphane (SFN) on the EMT and fibrosis using an in vitro transforming growth factor (TGF)-β1-induced model and an in vivo bleomycin (BLM)-induced model.MethodsIn vitro studies, cell viability, and cytotoxicity were measured using a Cell Counting Kit-8. The functional TGF-β1-induced EMT and fibrosis were assessed using western blotting and a quantitative real-time polymerase chain reaction. The lungs were analyzed histopathologically in vivo using hematoxylin and eosin and Masson's trichrome staining. The BLM-induced fibrosis was characterized by western blotting and immunohistochemical analyses for fibronectin, TGF-β1, E-cadherin (E-cad), and α-smooth muscle actin (SMA) in lung tissues.ResultsSFN reversed mesenchymal-like changes induced by TGF-β1 and restored cells to their epithelial-like morphology. The results confirmed that the expression of the epithelial marker, E-cadherin, increased after SFN treatment, while expression of the mesenchymal markers, N-cadherin, vimentin, and α-SMA decreased in A549 cells after SFN treatment. In addition, SFN inhibited TGF-β1-induced mRNA expression of the EMT-related transcription factors, Slug, Snail, and Twist. The SFN treatment attenuated TGF-β1-induced expression of fibrosis-related proteins, such as fibronection, collagen I, collagen IV, and α-SMA in MRC-5 cells. Furthermore, SFN reduced the TGF-β1-induced phosphorylation of SMAD2/3 protein in A549 cells and MRC-5 cells. BLM induced fibrosis in mouse lungs that was also attenuated by SFN treatment, and SFN treatment decreased BLM-induced fibronectin expression, TGF-β1 expression, and the levels of collagen I in the lungs of mice.ConclusionsSFN showed a significant anti-fibrotic effect in TGF-β-treated cell lines and BLM-induced fibrosis in mice. These findings showed that SFN has anti-fibrotic activity that may be considered in the treatment of IPF.

Project description:OBJECTIVE:To study the anti- fibrotic effect of human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-EXOs) and explore the mechanism. METHODS:Twenty-four C57 BL/6 mice were divided into 4 groups (n=6), including the control group treated with intratracheal injection of saline (3 mg/kg); lung fibrosis model group with intratracheal injection of 1.5 mg/mL bleomycin solution (prepared with saline, 3 mg/kg); EXOs1 group with intratracheal injection of 1.5 mg/mL bleomycin solution (3 mg/kg) and hUCMSC-EXOs (100 ?g/250 ?L, given by tail vein injection on the next day after modeling); and EXOs2 group with intratracheal injection of 1.5 mg/mL bleomycin solution (3 mg/kg) and hUCMSC-EXOs (100 ?g/250 ?L, given by tail vein injection on the 10th day after modeling). At 21 days after modeling, pulmonary index, lung tissue pathology and collagen deposition in the mice were assessed using HE staining and Masson staining. The expression level of TGF-?1 was detected using ELISA, and vimentin, E-cadherin and phosphorylated Smad2/3 (p-Smad2/3) were detected using immunohistochemical staining. CCK8 assay was used to evaluate the effect of hUCMSCEXOs on the viability of A549 cells, and Western blotting was used to detect the expression levels of p-Smad2/3, vimentin, and E-cadherin in the cells. RESULTS:Compared with those in the model group, the mice treated with hUCMSC-EXOs showed significantly reduced the pulmonary index (P < 0.05), collagen deposition, lung tissue pathologies, lowered expressions of TGF-?1 (P < 0.05), vimentin, and p-Smad2/3 and increased expression of E-cadherin. hUCMSC-EXOs given on the second day produced more pronounced effect than that given on the 11th day (P < 0.05). CCK8 assay results showed that hUCMSC-EXOs had no toxic effects on A549 cells (P > 0.05). Western blotting results showed that hUCMSC-EXOs treatment significantly increased the expression of E-cadherin and decreased the expressions of p-Smad2/3 and vimentin in the cells. CONCLUSIONS:hUCMSC-EXOs can alleviate pulmonary fibrosis in mice by inhibiting epithelialmesenchymal transition activated by the TGF-?1/Smad2/3 signaling pathway, and the inhibitory effect is more obvious when it is administered on the second day after modeling.

Dataset Information

Astragalus polysaccharides attenuate pulmonary fibrosis by inhibiting the epithelial-mesenchymal transition and NF-?B pathway activation.

Publications

Astragalus polysaccharides attenuate pulmonary fibrosis by inhibiting the epithelial-mesenchymal transition and NF-κB pathway activation.

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