Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation

• Published in: Cell death & disease Vol. 11; no. 11; p. 978
• Main Authors: Peng, Ling, Wen, Li, Shi, Qing-Feng, Gao, Feng, Huang, Bin, Meng, Jie, Hu, Cheng-Ping, Wang, Chang-Ming
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.11.2020; Springer Nature B.V
• Subjects: 692/699; 692/699/1785; Animals; Antibodies; Apigenin - pharmacology; Apigenin - therapeutic use; Biochemistry; Biomedical and Life Sciences; Caspase-1; Caspase-11; Cell Biology; Cell Culture; E-cadherin; Epithelial-Mesenchymal Transition; Extracellular matrix; Fibronectin; Fibrosis; Gelatinase A; Gelatinase B; Glucuronates - pharmacology; Glucuronates - therapeutic use; IL-1β; Immunology; Inflammation; Inflammation - drug therapy; Interleukin 18; Life Sciences; Lung diseases; Male; Matrix metalloproteinase; Mesenchyme; Metalloproteinase; Mice; N-Cadherin; NF-kappa B - antagonists & inhibitors; NF-κB protein; Pulmonary fibrosis; Pulmonary Fibrosis - genetics; Transfection; Vimentin
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-020-03178-2

Idiopathic pulmonary fibrosis (IPF) is featured with inflammation and extensive lung remodeling caused by overloaded deposition of extracellular matrix. Scutellarin is the major effective ingredient of breviscapine and its anti-inflammation efficacy has been reported before. Nevertheless, the impact of scutellarin on IPF and the downstream molecular mechanism remain unclear. In this study, scutellarin suppressed BLM-induced inflammation via NF-κB/NLRP3 pathway both in vivo and in vitro. BLM significantly elevated p-p65/p65 ratio, IκBα degradation, and levels of NLRP3, caspase-1, caspase-11, ASC, GSDMD Nterm , IL-1β, and IL-18, while scutellarin reversed the above alterations except for that of caspase-11. Scutellarin inhibited BLM-induced epithelial–mesenchymal transition (EMT) process in vivo and in vitro. The expression levels of EMT-related markers, including fibronectin, vimentin, N-cadherin, matrix metalloproteinase 2 (MMP-2) and MMP-9, were increased in BLM group, and suppressed by scutellarin. The expression level of E-cadherin showed the opposite changes. However, overexpression of NLRP3 eliminated the anti-inflammation and anti-EMT functions of scutellarin in vitro. In conclusion, scutellarin suppressed inflammation and EMT in BLM-induced pulmonary fibrosis through NF-κB/NLRP3 signaling.