title: Inflammatory Gene Expression Upon TGF-β1-Induced p38 Activation in Primary Dupuytren's Disease Fibroblasts.
abstract: OBJECTIVE
  Inflammation is an underlying mechanism behind fibrotic processes and differentiation of cells into myofibroblasts. Presented study therefore provides new data on activation of autoimmune and inflammatory immune response genes that accompany activation of p38 and cell differentiation in primary cells derived from Dupuytren's disease (DD) patients.
  
  
  METHODS
  Primary non-Dupuytren's disease cells (ND) were isolated from macroscopically unaffected palmar fascia adjacent to diseased tissue obtained from patients diagnosed with the last stage of DD and cultured in vitro. Gene expression, collagen gel contraction assay and analysis of secreted proteins were performed in ND cells treated with TGF-β1 and/or inhibitor of p38 phosphorylation.
  
  
  RESULTS
  During differentiation of ND fibroblasts, increased expression of immune response genes PAI-1, TIMP-1, CCL11, and IL-6 was found. These changes were accompanied by increased cell contractility and activation of p38 and its target kinase MK2. Inhibition of p38 phosphorylation reversed these processes in vitro.
  
  
  CONCLUSIONS
  TGF-β1 induced p38 phosphorylation in ND cells grown from macroscopically unaffected palmar fascia adjacent to diseased tissue from DD patients. This was accompanied by activation of the cytokine genes CCL-11 and IL-6 and secretion of extracellular matrix regulatory proteins PAI-1 and TIMP-1. A combined approach directed toward inflammation and p38 MAPK-mediated processes in DD might be considered for improving management of DD patients and prevention of recurrence.
authors.affiliation: Division of Molecular Medicine, Ruer Bošković Institute Zagreb, Croatia.
authors.forename: Maro
authors.initials: M
authors.lastname: Bujak
authors.affiliation: Department of Biotechnology, Centre for High-Throughput Technologies, University of Rijeka Rijeka, Croatia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Ratkaj
authors.affiliation: Department of Biotechnology, Centre for High-Throughput Technologies, University of Rijeka Rijeka, Croatia.
authors.forename: Elitza
authors.initials: E
authors.lastname: Markova-Car
authors.affiliation: Clinic for Surgery, Department for Plastic and Reconstructive Surgery, University Hospital Centre Rijeka Rijeka, Croatia.
authors.forename: Davor
authors.initials: D
authors.lastname: Jurišić
authors.affiliation: Division of Molecular Medicine, Ruer Bošković Institute Zagreb, Croatia.
authors.forename: Anita
authors.initials: A
authors.lastname: Horvatić
authors.affiliation: Division of Molecular Medicine, Ruer Bošković Institute Zagreb, Croatia.
authors.forename: Srđan
authors.initials: S
authors.lastname: Vučinić
authors.affiliation: Faculty of Engineering and Centre for Advanced Computing and Modelling, University of Rijeka Rijeka, Croatia ; Centre for Advanced Computing and Modelling, University of Rijeka Rijeka, Croatia.
authors.forename: Jonatan
authors.initials: J
authors.lastname: Lerga
authors.affiliation: Division of Molecular Medicine, Ruer Bošković Institute Zagreb, Croatia.
authors.forename: Mirela
authors.initials: M
authors.lastname: Baus-Lončar
authors.affiliation: Department of Biotechnology, Centre for High-Throughput Technologies, University of Rijeka Rijeka, Croatia.
authors.forename: Krešimir
authors.initials: K
authors.lastname: Pavelić
authors.affiliation: Department of Biotechnology, Centre for High-Throughput Technologies, University of Rijeka Rijeka, Croatia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Kraljević Pavelić
keywords: MK2 kinase; extracellular-matrix; inflammatory genes; myofibroblasts; p38 MAPK