Astragaloside IV restrains pulmonary fibrosis progression via the circ_0008898/miR‐211‐5p/HMGB1 axis

Abstract Pulmonary Fibrosis (PF) is a fatal lung disease with complicated pathogenesis. Astragaloside IV (ASV) has been discovered to alleviate PF progression, and the potential molecular mechanism of ASV in the development of PF need to be further clarified. Bleomycin (BLM) was used to construct PF in vivo model. Expression levels of circ_0008898, miR‐211‐5p, high mobility group protein B1 (HMGB1), alpha smooth muscle Actin (α‐SMA) and Collagen I were examined by Quantitative real time polymerase chain reaction (qRT‐PCR) and western blot. Cell survival was analyzed using Cell Counting Kit‐8 (CCK‐8) and EdU (5‐ethynyl‐2′‐deoxyuridine) assay. The invasion abilities were investigated by transwell assay. The levels of inflammatory factors were tested via using Enzyme‐linked immunosorbent assay (ELISA). The relationship between circ_0008898 or HMGB1 and miR‐211‐5p was identified by dual‐luciferase reporter assay. The results showed that ASV attenuated BLM‐induced pulmonary fibrosis in vivo. In vitro study, ASV alleviated TGF‐β1‐induced fibrogenesis in HFL1 cells. Circ_0008898 was increased in TGF‐β1‐induced HFL1 cells. ASV‐induced impacts were abrogated by circ_0008898 overexpression in TGF‐β1‐induced HFL1 cells. Mechanistically, circ_0008898 competitively bound to miR‐211‐5p to increase the expression of its target HMGB1. MiR‐211‐5p deficiency rescued ASV‐mediated effects in TGF‐β1‐induced HFL1 cells. In addition, HMGB1 overexpression partially overturned circ_0008898 interference‐induced impacts in HFL1 cells upon TGF‐β1 treatment. In conclusion, our work manifested that ASV hindered PF process by mediating the circ_0008898/miR‐211‐5p/HMGB1 network.