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Transforming growth factor-\u03b2 and keratinocyte growth factor (KGF), together with fibronectin and \u03b15\u03b21 integrin, were suggested to play a crucial role in the pathogenesis of psoriasis by influencing inflammation and keratinocyte hyperproliferation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To investigate the expression of KGF, fibroblast growth factor receptor (FGFR)2, fibronectin (FN) and extra domain A (EDA)-positive FN in healthy and nonlesional psoriatic skin, and to study the effect of KGF on the regulation of FN and EDA+FN production by fibroblasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Healthy, nonlesional psoriatic skin and lesional psoriatic skin were immunostained for \u03b15 integrin, KGF, FGFR2, EDA+FN and signal transducer and activator of transcription (STAT)1. KGF-treated cell cultures were analysed for FN and EDA+FN mRNA and protein by real-time reverse-transcriptase polymerase chain reaction and flow cytometry, respectively. The major downstream signalling of KGF was investigated by blocking experiments using inhibitors of mitogen-activated protein kinase (MAPK) kinase (MEK1), AKT1\/2, STAT1 and STAT3.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression of \u03b15 integrin, EDA+FN, KGF and its receptor FGFR2 is elevated in psoriatic nonlesional skin compared with healthy skin. KGF mildly induced EDA+FN, but not FN expression in healthy fibroblasts through MAPK signalling. Fibroblasts express the FGFR2-IIIc splice variant. STAT1 negatively regulates both FN and EDA+FN expression in healthy fibroblasts, and this regulation is compromised in fibroblasts derived from nonlesional psoriatic dermis. We detected active STAT1 in healthy and lesional skin, similarly to a previous report. However, in the nonlesional skin STAT1 activation was absent in tissues far away from lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The production of FN and EDA+FN by fibroblasts and the signalling of STAT1 are abnormally regulated in psoriatic nonlesional skin.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bjd.14219","type":"journal-article","created":{"date-parts":[[2015,10,16]],"date-time":"2015-10-16T04:42:40Z","timestamp":1444970560000},"page":"533-541","source":"Crossref","is-referenced-by-count":49,"title":["Abnormal regulation of fibronectin production by fibroblasts in psoriasis"],"prefix":"10.1093","volume":"174","author":[{"given":"B.","family":"Gub\u00e1n","sequence":"first","affiliation":[{"name":"Department of Dermatology and Allergology University of Szeged Kor\u00e1nyi fasor 6 H-6720 Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Vas","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology University of Szeged Kor\u00e1nyi fasor 6 H-6720 Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Balog","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology University of Szeged Kor\u00e1nyi fasor 6 H-6720 Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Manczinger","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology University of Szeged Kor\u00e1nyi fasor 6 H-6720 Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Bebes","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology University of Szeged Kor\u00e1nyi fasor 6 H-6720 Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Groma","sequence":"additional","affiliation":[{"name":"MTA-SZTE Dermatological Research Group University of Szeged Kor\u00e1nyi fasor 6 H-6720 Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Sz\u00e9ll","sequence":"additional","affiliation":[{"name":"MTA-SZTE Dermatological Research Group University of Szeged Kor\u00e1nyi fasor 6 H-6720 Szeged Hungary"},{"name":"Department of Medical Genetics University of Szeged Kor\u00e1nyi fasor 6 H-6720 Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Kem\u00e9ny","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology University of Szeged Kor\u00e1nyi fasor 6 H-6720 Szeged Hungary"},{"name":"MTA-SZTE Dermatological Research Group University of Szeged Kor\u00e1nyi fasor 6 H-6720 Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Bata-Cs\u00f6rg\u0151","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology University of Szeged Kor\u00e1nyi fasor 6 H-6720 Szeged Hungary"},{"name":"MTA-SZTE Dermatological Research Group University of Szeged Kor\u00e1nyi fasor 6 H-6720 Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,3,1]]},"reference":[{"key":"2023033115535209900_","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1111\/j.1365-2133.2005.06645.x","article-title":"Psoriasis: dysregulation of innate immunity","volume":"152","author":"Bos","year":"2005","journal-title":"Br J Dermatol"},{"key":"2023033115535209900_","doi-asserted-by":"crossref","first-page":"1783","DOI":"10.1172\/JCI115782","article-title":"Expression, topography, and function of integrin receptors are severely altered in keratinocytes from involved and uninvolved psoriatic skin","volume":"89","author":"Pellegrini","year":"1992","journal-title":"J Clin Invest"},{"key":"2023033115535209900_","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1172\/JCI171","article-title":"Fibronectin and \u03b15 integrin regulate keratinocyte cell cycling. 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