Abnormal regulation of fibronectin production by fibroblasts in psoriasis

Barbara Gubán, K. Vas, Z. Balog, M. Manczinger, A. Bebes, G. Groma, M. Széll, L. Kemény, Z. Bata-Csörgö

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background Data indicate that in psoriasis, abnormalities are already present in nonlesional skin. Transforming growth factor-β and keratinocyte growth factor (KGF), together with fibronectin and α5β1 integrin, were suggested to play a crucial role in the pathogenesis of psoriasis by influencing inflammation and keratinocyte hyperproliferation. Objectives 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. Methods Healthy, nonlesional psoriatic skin and lesional psoriatic skin were immunostained for α5 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. Results The expression of α5 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. Conclusions The production of FN and EDA+FN by fibroblasts and the signalling of STAT1 are abnormally regulated in psoriatic nonlesional skin.

Original languageEnglish
Pages (from-to)533-541
Number of pages9
JournalBritish Journal of Dermatology
Volume174
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

ASJC Scopus subject areas

  • Dermatology

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