Dataset Information

Citrus alkaline extracts improve LPS-induced pulmonary fibrosis via epithelial mesenchymal transition signals.

ABSTRACT:

Background

Acute respiratory distress syndrome (ARDS) is a serious life threatening clinical critical illness. ARDS-related pulmonary fibrosis is a common complication of ARDS. The occurrence of early pulmonary fibrosis indicates a higher incidence and mortality of multiple organ failure. LPS-induced ARDS-related pulmonary fibrosis model in mice was established in this study. And we have explored the anti-pulmonary fibrosis effects and molecular mechanisms of the Citrus Alkaline Extracts (CAE) in vivo and in vitro.

Methods

Pulmonary fibrosis mouse model and lung epithelial cell injury model were established in this study. H&E, Masson and Sirius Red staining were used to estimate lung tissue damage. Immunohistochemistry and western blotting were used to analyze proteins expression. Protein-protein interaction was observed by Co-Immunoprecipitation. Systemic impact of CAE on signaling pathway was examined by RNA-seq.

Results

Through H&E, Masson and Sirius Red staining, it was convincingly indicated that therapeutic administration of CAE alleviated lung injury and fibrosis, while pretreated administration of CAE showed weak improvement. In vitro experiments showed that CAE had dual regulation to E-cadherin and N-cadherin, the important indicators of epithelial-mesenchymal transition (EMT). And it was further demonstrated that CAE reversed TGF-β1-induced EMT mainly through Wnt/β-catenin, Stat3/6 and COX2/PGE2 signals. Through RNA-Seq, we discovered important mechanisms by which CAE exerts its therapeutic effect. And network pharmacology analysis demonstrated core potential targets of CAE in EMT.

Conclusion

Thus, this study provides new therapeutic effects of CAE in anti-fibrosis, and offers potential mechanisms for CAE in LPS-induced pulmonary fibrosis.

SUBMITTER: Junjie L

PROVIDER: S-EPMC10226443 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Publications

Citrus alkaline extracts improve LPS-induced pulmonary fibrosis via epithelial mesenchymal transition signals.

Junjie Li L Cheng Gu G Kangkang Luo L Yu Li L Zhiyao Yuan Y Xudong Wu W Xianmei Zhou Z Xiaomin Lu L

Chinese medicine 20230529 1

<h4>Background</h4>Acute respiratory distress syndrome (ARDS) is a serious life threatening clinical critical illness. ARDS-related pulmonary fibrosis is a common complication of ARDS. The occurrence of early pulmonary fibrosis indicates a higher incidence and mortality of multiple organ failure. LPS-induced ARDS-related pulmonary fibrosis model in mice was established in this study. And we have explored the anti-pulmonary fibrosis effects and molecular mechanisms of the Citrus Alkaline Extracts ...[more]

PMID: 37248506

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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.

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Dataset Information

Citrus alkaline extracts improve LPS-induced pulmonary fibrosis via epithelial mesenchymal transition signals.

Background

Methods

Results

Conclusion

Publications

Citrus alkaline extracts improve LPS-induced pulmonary fibrosis via epithelial mesenchymal transition signals.

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