Astragaloside IV attenuates TGF-β-mediated epithelial-mesenchymal transition of pulmonary fibrosis via suppressing NLRP3 expression in vitro.

Abstract

Pulmonary fibrosis (PF) is a severe chronic disease. Although astragaloside IV (ASV) is known to have therapeutic effects on PF, the therapeutic targets of ASV require further study. This study was designed to elucidate the regulatory effect of ASV on PF via NLRP3. PF was triggered by transforming growth factor-β (TGF-β) in vitro. The relative activity of TGF-β was measured by luciferase reporter assay. Protein levels were determined by western blotting assay. The NLRP3 expression was analyzed using immunofluorescence analysis. mRNA levels were detected by qRT-PCR. MTT assay was performed to determine cell viability. Wound healing and transwell assays were conducted to investigate cell migration and invasion. We found that ASV markedly suppressed TGF-β activity, Smad2/3 and NLRP3 protein expression levels. ASV inhibited cell viability, migration and invasion ability. Moreover, ASV mediated downregulation of N-cadherin and Snail and upregulation of E-cadherin, which further suppressed the epithelial-mesenchymal transition (EMT). However, overexpression of NLRP3 reversed the effects of ASV and promoted Collagen I, Collagen II and α-SMA protein expressions. In conclusion, ASV efficiently retarded PF progress via suppressing NLRP3 expression in vitro.