AMPK Inhibits TGF‐β1–Induced Extra Cellular Matrix Production in Nasal Polyp‐Derived Fibroblast

Abstract

Objectives: Adenosine monophosphate-activated protein kinase (AMPK) is known to inhibit fibrogenic responses in many cells by targeting TGF-Î21-Smad signaling. The purpose of this study was to investigate the effect of AMPK on TGF-Î21-induced myofibroblast differentiation and ECM production and to determine the underlying mechanism for the action of AMPK in nasal polyp-derived fibroblasts (NPDFs). Methods: NPDFs were incubated with TGF-β1 and treated with the activator of AMPK (metformin) or inhibitor of AMPK (compound C). To determine the proliferation rate of nasal fibroblasts, MTT assay was performed. The expression levels of α-smooth muscle actin and fibronectin were determined by reverse transcription polymerase chain reaction (RT-PCR), Western blotting and immunofluorescent staining. Phosphorylation of AMPK and phosphorylation of Smad2/3 were evaluated by Western blot analysis. Results: In TGF-β1-induced NPDFs, metformin inhibited the expression of α-SMA and fibronectin, as confirmed by both RT-PCR and Western blotting analysis. Metformin increased the phosphorylation of AMPK and expression levels of α-SMA and fibronectin, and compound C reversed these effects. Metformin inhibited TGF-β1-induced phosphorylation of Smad2/3. Conclusions: This study showed that AMPK inhibited TGF-β1-induced ECM production in NPDFs via the Smad2/3 pathway. AMPK can be a therapeutic target for the prevention of ECM remodeling in nasal polyps.