Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-?B/NLRP3-mediated epithelial-mesenchymal transition and inflammation.

ABSTRACT: 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-?B/NLRP3 pathway both in vivo and in vitro. BLM significantly elevated p-p65/p65 ratio, I?B? degradation, and levels of NLRP3, caspase-1, caspase-11, ASC, GSDMDNterm, IL-1?, 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-?B/NLRP3 signaling.

SUBMITTER: Peng L 

PROVIDER: S-EPMC7666141 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature