{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T17:20:58Z","timestamp":1784049658321,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,9,11]],"date-time":"2014-09-11T00:00:00Z","timestamp":1410393600000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81101430"],"award-info":[{"award-number":["81101430"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81171695"],"award-info":[{"award-number":["81171695"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Scientific Research Fund of Zhejiang Provincial Health Department, China","award":["Y2011KYA109"],"award-info":[{"award-number":["Y2011KYA109"]}]},{"name":"Guangzhou City Science and Technology Project","award":["2012J4100044"],"award-info":[{"award-number":["2012J4100044"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The proliferation of human skin dermal fibroblasts (HDFs) is a critical step in skin fibrosis, and transforming growth factor\u2010beta1 (TGF\u2010<jats:italic>\u03b2<\/jats:italic>1) exerts pro\u2010oxidant and fibrogenic effects on HDFs. In addition, the oxidative stress system has been implicated in the pathogenesis of skin disease. However, the role of NADPH oxidase as a mediator of TGF\u2010<jats:italic>\u03b2<\/jats:italic>1\u2010induced effects in HDFs remains unknown. Thus, our aim was to investigate the role of NADPH in human skin dermal fibroblasts. Primary fibroblasts were cultured and pretreated with various stimulants. Real\u2010time Q\u2010PCR and Western blotting analyses were used for m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> and protein detection. In addition, siRNA technology was applied for gene knock\u2010down analysis. Hydrogen peroxide production and 2\u2032,7\u2032\u2010dichlorofluorescein diacetate (DCFDA) measurement assay were performed. Here, our findings demonstrated that HDFs express key components of non\u2010phagocytic NADPH oxidase m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>. TGF\u2010<jats:italic>\u03b2<\/jats:italic>1 induced NOX2 and reactive oxygen species formation via NADPH oxidase activity. In contrast, NOX3 was barely detectable, and other NOXs did not display significant changes. In addition, TGF\u2010<jats:italic>\u03b2<\/jats:italic>1 phosphorylated MAPKs and increased activator protein\u20101 (AP\u20101) in a redox\u2010sensitive manner, and NOX2 suppression inhibited baseline and TGF\u2010<jats:italic>\u03b2<\/jats:italic>1\u2010mediated stimulation of Smad2 phosphorylation. Moreover, TGF\u2010<jats:italic>\u03b2<\/jats:italic>1 stimulated cell proliferation, migration, collagen I and fibronectin expression, and b<jats:styled-content style=\"fixed-case\">FGF<\/jats:styled-content> and PAI\u20101 secretion: these effects were attenuated by diphenylene iodonium (DPI), an NADPH oxidase inhibitor, and NOX2 siRNA. Importantly, NOX2 siRNA suppresses collagen production in primary keloid dermal fibroblasts. These findings provide the proof of concept for NADPH oxidase as a potential target for the treatment of skin fibrosis.<\/jats:p>","DOI":"10.1111\/exd.12479","type":"journal-article","created":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T09:17:04Z","timestamp":1404206224000},"page":"639-644","source":"Crossref","is-referenced-by-count":28,"title":["<scp>NADPH<\/scp> oxidase\u20102 is a key regulator of human dermal fibroblasts: a potential therapeutic strategy for the treatment of skin fibrosis"],"prefix":"10.1111","volume":"23","author":[{"given":"Guo\u2010You","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Hand and Plastic Surgery The Second Affiliated Hospital of Wenzhou Medical University Wenzhou China"},{"name":"Department of Plastic and Reconstructive Surgery Shanghai Ninth People's Hospital of Shanghai Jiaotong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang\u2010Cai","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Dermatology Huang\u2010Pu Hospital of the First Affiliated Hospital Sun Yat\u2010Sen Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery of the Third Affiliated Hospital of Henan University of Science and Technology Luoyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi\u2010Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hand and Plastic Surgery The Second Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An\u2010Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hand and Plastic Surgery The Second Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Hand and Plastic Surgery The Second Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da\u2010Mu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Hand and Plastic Surgery The Second Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing\u2010Quan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hand and Plastic Surgery The Second Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery Guangzhou General Hospital of Guangzhou Military Command PLA Guangzhou China"},{"name":"The Key Laboratory of Trauma Treatment and Tissue Repair of Tropical Area PLA Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery The First Affiliated Hospital of Bengbu Medical College Bengbu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Yang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Hand and Plastic Surgery The Second Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hand and Plastic Surgery The Second Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,9,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.5.1464"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-2494.2008.00454.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-009-0959-1"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2010.10111.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1462399403005817"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/1566523044578004"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2008.08989.x"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2002.126078"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90489-D"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81817-6"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/383168a0"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90152-3"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2006.09.006"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2004.06.010"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700960"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700820"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200111)44:11<2653::AID-ART445>3.0.CO;2-1"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/exd.12157"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00044.2005"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.86.5.494"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.26.14483"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18212"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2009020146"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(03)00194-4"},{"key":"e_1_2_8_26_1","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1161\/atvb.22.1.4","volume":"22","author":"Weintraub N L","year":"2002","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2009.00880.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2007.06.009"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-007-0825-y"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.36.23611"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501654200"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00726.2001"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61252-7"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.3.2099"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2005"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00758.2002"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000187457.24338.3D"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2005.06.008"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20698"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/jid.2008.337"}],"container-title":["Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fexd.12479","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/exd.12479","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T17:55:05Z","timestamp":1696355705000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/exd.12479"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9]]},"references-count":39,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2014,9]]}},"alternative-id":["10.1111\/exd.12479"],"URL":"https:\/\/doi.org\/10.1111\/exd.12479","archive":["Portico"],"relation":{},"ISSN":["0906-6705","1600-0625"],"issn-type":[{"value":"0906-6705","type":"print"},{"value":"1600-0625","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9]]}}}