AMPK regulates the anti-pulmonary fibrosis effects of tracheloside

Abstract

Idiopathic pulmonary fibrosis (IPF) presents limited therapeutic options that often involve severe side effects, making the development of innovative treatments essential. While tracheloside (TCL) demonstrates various medicinal properties, its mechanism of action remains incompletely understood. This study examines TCL’s effects and mechanisms on bleomycin (BLM)-induced pulmonary fibrosis in mice. A BLM-induced pulmonary fibrosis model was established in vivo to assess TCL’s anti-fibrotic and anti-oxidative properties. In vitro studies utilized transforming growth factor-β (TGF-β) and matrix stiffness-induced myofibroblast differentiation models to investigate TCL’s mechanism. The results demonstrated that TCL inhibited BLM-induced pulmonary fibrosis. In vitro experiments revealed that TCL activated adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), suppressed TGF-β or matrix stiffness-induced myofibroblast differentiation, decreased nicotinamide adenine dinucleotide phosphate oxidase isoform 4 (NOX4) expression, enhanced antioxidant enzyme expression, and mitigated oxidative stress. Additionally, activated AMPK inhibited NOX4 expression and, notably, reduced NOX4 activation through competitive binding to p22 phox. The findings indicate that TCL alleviates TGF-β or matrix stiffness-induced myofibroblast differentiation and oxidative stress via the AMPK/NOX4 signaling pathway, thereby exhibiting anti-fibrotic and anti-oxidative effects. This research presents novel insights into AMPK’s regulation of NOX4.

Keywords

Tracheloside / AMPK / Oxidative stress / Pulmonary fibrosis / NOX4

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