{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:16:25Z","timestamp":1777385785297,"version":"3.51.4"},"reference-count":27,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Am J Rhinol\ufffdAllergy"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Rapamycin has antiproliferative and antifibrogenic effects in vitro and in vivo. The purpose of this study was to evaluate the effects of rapamycin on transforming growth factor (TGF) beta 1 induced myofibroblast differentiation (alpha smooth-muscle actin [SMA]), extracellular matrix production, and collagen contraction in nasal polyp\u2013derived fibroblasts (NPDF). The underlying molecular mechanisms of rapamycin were also determined in NPDFs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>NPDFs were grown in culture and transformed into myofibroblasts by using TGF beta 1 (5 ng\/mL). For cytotoxicity evaluation, a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay was used. Expression levels of alpha SMA, phosphorylated phosphatidylinositol 3-kinase (PI3K), and phosphorylated mammalian target of rapamycin (mTOR) were determined by using Western blot, reverse transcription\u2013polymerase chain reaction, and immunofluorescence staining. The total amount of collagen was analyzed by using the Sircol collagen assay, and contractile activity was measured with a collagen gel contraction assay. Silencing mTOR with mTOR-specific small interference RNA was determined by using reverse transcription\u2013polymerase chain reaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Whereas rapamycin (range, 0\u2013400 nM) had no significant cytotoxic effects on TGF beta 1 induced NPDFs, it significantly reduced the expression levels of alpha\u2013SMA in TGF beta 1 induced NPDFs in a dose-dependent manner. TGF beta 1 induced collagen production and collagen contraction were significantly inhibited by rapamycin treatment. Rapamycin also attenuated the TGF beta 1 induced activation of PI3K and mTOR, and its inhibitory effects were similar to those of mTOR silencing and a specific PI3K inhibitor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Rapamycin inhibited TGF beta 1 induced myofibroblast differentiation, extracellular matrix production, and collagen contraction through the PI3K\/mTOR signal pathways in NPDFs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2500\/ajra.2016.30.4389","type":"journal-article","created":{"date-parts":[[2016,11,22]],"date-time":"2016-11-22T15:15:33Z","timestamp":1479827733000},"page":"e211-e217","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["Rapamycin Inhibits Transforming Growth Factor Beta 1 Induced Myofibroblast Differentiation\n                    <i>via<\/i>\n                    the Phosphorylated-Phosphatidylinositol 3-Kinase Mammalian Target of Rapamycin Signal Pathways in Nasal Polyp\u2013Derived Fibroblasts"],"prefix":"10.1177","volume":"30","author":[{"given":"Dong-Yn","family":"Ko","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery Seoul, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Min","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery Seoul, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Young","family":"Um","sequence":"additional","affiliation":[{"name":"Division of Brain Korea 21 Program for Biomedical Science Seoul, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byungjin","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery Seoul, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Il-Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery Seoul, South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heung-Man","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery Seoul, South Korea"},{"name":"Division of Brain Korea 21 Program for Biomedical Science Seoul, South Korea"},{"name":"lnstitute for Korea University Medical Devices Support Center, Guro Hospital, Korea University College of Medicine, Seoul, South 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