{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:24:26Z","timestamp":1790400266942,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,12,18]],"date-time":"2013-12-18T00:00:00Z","timestamp":1387324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2013,12,18]],"date-time":"2013-12-18T00:00:00Z","timestamp":1387324800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Objects<\/jats:title>\n                    <jats:p>Metformin is widely used to treat type 2 diabetes mellitus, and adenosine monophosphate\u2013activated 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\u2010\u03b21\u2013induced myofibroblast differentiation (\u03b1\u2010smooth muscle actin [\u03b1\u2010SMA]) and extracellular matrix (ECM) production and to determine the underlying mechanism of the action of metformin in nasal polyp\u2013derived fibroblasts (NPDFs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Study Design<\/jats:title>\n                    <jats:p>Basic research.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>The rhinology laboratory of Korea University Guro Hospital, Seoul, Korea.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>NPDFs from 7 patients were incubated with TGF\u2010\u03b21 and treated with metformin or compound C, an inhibitor of AMPK. To determine the proliferation rate of nasal fibroblasts, a 3\u2010(4,5\u2010dimethylthiazol\u20102\u2010yl)\u20102,5\u2010diphenyl tetrazolium bromide assay was performed. The expression levels of \u03b1\u2010SMA and fibronectin were determined by reverse transcription\u2013polymerase chain reaction (RT\u2010PCR), Western blotting, and immunofluorescent staining. Phosphorylation of AMPK and phosphorylation of Smad2\/3 were evaluated by Western blot analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In TGF\u2010\u03b21\u2013induced NPDFs, metformin inhibited the expression of \u03b1\u2010SMA and fibronectin, as confirmed by both RT\u2010PCR and Western blot analysis. Metformin increased the phosphorylation of AMPK and the expression levels of \u03b1\u2010SMA and fibronectin. However, compound C reversed these effects. Metformin inhibited TGF\u2010\u03b21\u2013induced phosphorylation of Smad2\/3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study showed that metformin inhibits TGF\u2010\u03b21\u2013induced 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0194599813513880","type":"journal-article","created":{"date-parts":[[2013,12,19]],"date-time":"2013-12-19T00:05:13Z","timestamp":1387411513000},"page":"148-153","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Metformin Reduces TGF\u2010\u03b21\u2013Induced Extracellular Matrix Production in Nasal Polyp\u2013Derived Fibroblasts"],"prefix":"10.1002","volume":"150","author":[{"given":"Il\u2010Ho","family":"Park","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery Korea University College of Medicine Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010Young","family":"Um","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences Korea University Graduate School Seoul 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