Abstract
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.
Graphical Abstract
Funder
National Natural Science Foundation of China
Natural Science Foundation of Jiangsu Province
Fundamental Research Funds for the Central Universities
Publisher
Springer Science and Business Media LLC
Subject
Complementary and alternative medicine,Pharmacology
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