{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:29:07Z","timestamp":1787023747512,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Fibroblasts play a critical role during wound healing and chronic inflammation through the synthesis and assembly of extracellular matrix (ECM) molecules. These responses may be modulated by soluble cytokines and growth factors present in tissues. In the present study, we evaluate whether transforming growth factor\u2010\u03b21 (TGF\u2010\u03b21) and tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) modulate myofibroblastic differentiation and the production of ECM components.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    Primary cultures of human gingival fibroblasts (HGFs) were stimulated with recombinant TGF\u2010\u03b21 and TNF\u2010\u03b1. Protein levels of \u03b1\u2010smooth muscle actin (\u03b1\u2010SMA), type I collagen, heat shock protein\u201047 (HSP\u201047), fibronectin (FN), ED\u2010A\u2010FN, and periostin and activation of the Smad pathway were evaluated through Western blot analysis. \u03b1\u2010SMA and actin fibers were identified by immunofluorescence. TGF\u2010\u03b21, TNF\u2010\u03b1, and \u03b1\u2010SMA were identified by immunohistochemistry in biopsies of inflamed human gingival tissues. TGF\u2010\u03b21 activity was evaluated using a plasminogen activator inhibitor\u20101 (PAI\u20101) reporter transfected in HGFs.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    TGF\u2010\u03b21 stimulated the differentiation of myofibroblasts as evidenced by strong expression of \u03b1\u2010SMA and ED\u2010A\u2010FN. Moreover, TGF\u2010\u03b21 induced the production of type I collagen, HSP\u201047, FN, and periostin. Costimulation with TNF\u2010\u03b1 and TGF\u2010\u03b21 significantly reduced the expression of all the above\u2010mentioned proteins. TNF\u2010\u03b1 also inhibited the activation of the Smad2\/3 pathway and the activity of the PAI\u20101 reporter.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    TNF\u2010\u03b1 inhibits several cell responses induced by TGF\u2010\u03b21, including the differentiation of myofibroblasts, the activation of the Smad signaling pathway, and the production of key molecules involved in tissue repair, such as type I collagen, FN, and periostin. The interaction between cytokines may explain the delayed tissue repair observed in chronic inflammation of gingival tissues.\n                  <\/jats:p>","DOI":"10.1902\/jop.2012.120225","type":"journal-article","created":{"date-parts":[[2012,7,20]],"date-time":"2012-07-20T03:55:11Z","timestamp":1342756511000},"page":"683-693","source":"Crossref","is-referenced-by-count":35,"title":["Tumor Necrosis Factor\u2010\u03b1 Inhibits Transforming Growth Factor\u2010\u03b2\u2013Stimulated Myofibroblastic Differentiation and Extracellular Matrix Production in Human Gingival Fibroblasts"],"prefix":"10.1002","volume":"84","author":[{"given":"Rodrigo","family":"Arancibia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Oyarz\u00fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00e1s","family":"Tobar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricio C.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411006"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0757.1997.tb00199.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1982.tb02108.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.103.6.2787"},{"key":"e_1_2_6_6_1","first-page":"21","article-title":"Alpha\u2010smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing","volume":"63","author":"Darby I","year":"1990","journal-title":"Lab Invest"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm809"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65527-7"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700613"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.122.1.103"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.142.3.873"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.117.4.903"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1524-475X.2002.10406.x"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.24.11131-11144.2005"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12079-009-0057-3"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.2929"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)32345-7"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.17.10188"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12606979"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-051X.1995.tb00826.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.8.1745"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401189"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9969(90)90205-O"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345970760120501"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.114.1.131"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2007.01081.x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005310200"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700890"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.21.2.3641"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0757.2000.2240107.x"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-0825.1996.tb00217.x"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E08-10-0994"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.162488599"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910708600513"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345890680010301"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90395-S"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.52.37413"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.7.804"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001432-200404000-00004"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034509359125"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.050980"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-051X.1999.260606.x"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910708600409"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1601-0825.2003.02895.x"},{"key":"e_1_2_6_45_1","first-page":"144","article-title":"Differentiation repertoire of fibroblastic cells: Expression of cytoskeletal proteins as marker of phenotypic modulations","volume":"63","author":"Sappino AP","year":"1990","journal-title":"Lab Invest"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1177\/154405910608500207"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63764-9"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700097"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302339200"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.5.3514"}],"container-title":["Journal of Periodontology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1902\/jop.2012.120225","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1902\/jop.2012.120225","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/pdf\/10.1902\/jop.2012.120225","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T12:51:12Z","timestamp":1760878272000},"score":1,"resource":{"primary":{"URL":"https:\/\/aap.onlinelibrary.wiley.com\/doi\/10.1902\/jop.2012.120225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2013,5]]}},"alternative-id":["10.1902\/jop.2012.120225"],"URL":"https:\/\/doi.org\/10.1902\/jop.2012.120225","archive":["Portico"],"relation":{},"ISSN":["0022-3492","1943-3670"],"issn-type":[{"value":"0022-3492","type":"print"},{"value":"1943-3670","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5]]}}}