Platycodin D ameliorates ammonia‐induced pulmonary fibrosis by repressing TGF‐β1‐mediated extracellular matrix remodeling

Abstract

Ammonia can induce pulmonary fibrosis in humans and animals. Platycodin D (PLD) possesses various bioactive activities including anti‐fibrotic properties. In this study, we aimed to explore the activity and mechanism of PLD in pulmonary fibrosis induced by ammonia. The mouse model of ammonia‐induced lung fibrosis was established, and the role of PLD was assessed by H&E and Masson's trichrome staining. The differentially expressed genes (DEGs) were identified by RNA‐seq and subjected to GO and KEGG pathway analyses. BEAS‐2B cells were treated with NH4Cl alone or along with PLD. Results showed that PLD attenuated ammonia‐induced pulmonary inflammation and fibrosis in vivo. The extracellular matrix (ECM)‐receptor interaction pathway was predicted as a prominent pathway underlying the anti‐fibrotic function of PLD. In ammonia‐induced mouse models and NH4Cl‐treated BEAS‐2B cells, PLD could repress the activation of the TGF‐β1 pathway. By incubating lung fibroblast HFL1 cells with the conditioned medium of BEAS‐2B cells treated with NH4Cl alone or along with PLD, PLD was confirmed to attenuate NH4Cl‐induced ECM deposition in HFL1 cells. Our findings demonstrate that PLD exerts a protective function in ammonia‐induced pulmonary fibrosis by repressing TGF‐β1‐mediated ECM remodeling, suggesting the potential therapeutic value of PLD in this disease.