{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:25:19Z","timestamp":1780316719145,"version":"3.54.1"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,11,17]],"date-time":"2015-11-17T00:00:00Z","timestamp":1447718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Doxycycline has been shown to have antibacterial and anti\u2010inflammatory effects and suppresses collagen biosynthesis. The purpose of this study was to evaluate the effects of doxycycline on transforming growth factor (TGF)\u2010\u03b21\u2013induced myofibroblast differentiation and extracellular matrix production in nasal polyp\u2013derived fibroblasts (NPDFs). We also determined the molecular mechanisms of action for doxycycline.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>NPDFs were isolated from nasal polyps from 8 patients. Doxycycline was used to pretreat TGF\u2010\u03b21\u2013induced NPDFs. Cytotoxicity was evaluated using a 3\u2010(4,5\u2010dimethylthiazol\u20102yl)\u20102,5\u2010diphenyl\u2010tetrazolium bromide assay. Expression levels of \u03b1\u2013smooth muscle actin (SMA) and fibronectin were measured using Western blot, reverse\u2010transcription polymerase chain reaction, and immunofluorescence staining. Total collagen production was analyzed with the Sircol collagen assay, while mitogen\u2010activated protein kinase (MAPK) and NF\u2010\u03baB activation were determined using Western blot analysis. Luciferase assay was used to evaluate the transcriptional activity of NF\u2010\u03baB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Although doxycycline (0 to 40\u00a0\u03bcg\/mL) had no significant cytotoxic effects in TGF\u2010\u03b21\u2013induced NPDFs, it significantly reduced the expression levels of \u03b1\u2010SMA, fibronectin, and collagen in TGF\u2010\u03b21\u2013induced NPDFs in a dose\u2010dependent manner. Doxycycline also inhibited the TGF\u2010\u03b21\u2013induced activation of p38, c\u2010Jun NH<jats:sub>2<\/jats:sub>\u2010terminal kinase (JNK), and NF\u2010\u03baB, and its inhibitory effects were similar to those of the specific inhibitors for each.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Doxycycline has an inhibitory effect on TGF\u2010\u03b21\u2013induced myofibroblast differentiation and extracellular matrix production via the p38 and JNK\/NF\u2010\u03baB signal pathways in NPDFs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.21660","type":"journal-article","created":{"date-parts":[[2015,11,17]],"date-time":"2015-11-17T13:56:41Z","timestamp":1447768601000},"page":"256-263","source":"Crossref","is-referenced-by-count":14,"title":["Doxycycline inhibits TGF\u2010\u03b21\u2013induced extracellular matrix production in nasal polyp\u2013derived fibroblasts"],"prefix":"10.1002","volume":"6","author":[{"given":"Jae\u2010Min","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery Korea University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo\u2010Hoo","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Brain Korea 21 Program for Biomedical Science Korea University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il\u2010Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery Korea University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heung\u2010Man","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2013Head and Neck Surgery Korea University College of Medicine  Seoul South Korea"},{"name":"Division of Brain Korea 21 Program for Biomedical Science Korea University College of Medicine  Seoul South Korea"},{"name":"Research\u2010Driven Hospital, Korea University Guro Hospital Korea University College of Medicine  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,11,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.2500\/105065800781329573"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1472-9725.2003.00061.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082373"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2006.01.003"},{"key":"e_1_2_6_6_1","first-page":"381","article-title":"Effect of myofibroblast accumulation on the formation and development of nasal polyps","volume":"41","author":"Wang QP","year":"2006","journal-title":"Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.2741\/2031"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.11.3630-3633.2003"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1982.53.10.604"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2004.75.3.453"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.4103\/0970-2113.53231"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2010.12.003"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2010.01.037"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)01372-3"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-11787"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2010.02.020"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.2011.03931.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1916-0216-42-27"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02006"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200005043421807"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2012.10.003"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-0929"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-1273rev"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1228704"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.10.6504"}],"container-title":["International Forum of Allergy &amp; 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