Background and Objects. Metformin is widely used to treat type 2 diabetes mellitus, and adenosine monophosphate- activated protein kinase (AMPK) is thought to be the target that mediates its effects. Recently, it has been demonstrated that metformin has antifibrotic effects beyond its antihyperglycemic action. The purposes of this study were to investigate the effect of metformin on TGF-β1-induced myofibroblast differentiation (a-smooth muscle actin [α-SMA]) and extracellular matrix (ECM) production and to determine the underlying mechanism of the action of metformin in nasal polyp-derived fibroblasts (NPDFs). Study Design. Basic research. Setting. The rhinology laboratory of Korea University Guro Hospital, Seoul, Korea. Methods. NPDFs from 7 patients were incubated with TGFb1 and treated with metformin or compound C, an inhibitor of AMPK. To determine the proliferation rate of nasal fibroblasts, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay was performed. The expression levels of a-SMA 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 blot analysis. Metformin increased the phosphorylation of AMPK and the expression levels of α-SMA and fibronectin. However, compound C reversed these effects. Metformin inhibited TGF-β1-induced phosphorylation of Smad2/3. Conclusions. This study showed that metformin inhibits TGFβ1- induced myofibroblast differentiation and ECM production in NPDFs via the Smad2/3 pathway. AMPK can be a therapeutic target for the prevention of ECM remodeling in nasal polyps.
|Number of pages||6|
|Journal||Otolaryngology - Head and Neck Surgery (United States)|
|Publication status||Published - 2014 Jan|
- adenosine monophosphate-activated protein kinase
- nasal polyposis
ASJC Scopus subject areas