title: Elevated protein arginine methyltransferase 1 expression regulates fibroblast motility in pulmonary fibrosis.
abstract: OBJECTIVE
  Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by epithelial cell injury, fibroblast activation and excessive extracellular matrix deposition. Although protein arginine methyltransferase 1 (PRMT1) was found to regulate cell proliferation, differentiation and migration, its role in the development/progression of IPF has not yet been described.
  
  
  RESULTS
  Expression of PRMT1 was elevated in lung homogenates from IPF patients. Significant upregulation of PRMT1 expression was also observed in the lungs of bleomycin-treated mice. Immunohistochemical analysis revealed PRMT1-positive staining in fibroblasts/myofibroblasts and alveolar type II cells of IPF lungs and in fibrotic lesions of bleomycin-injured lungs. Fibroblasts isolated from IPF lungs demonstrated increased PRMT1 expression. Interleukin-4 (IL-4), a profibrotic cytokine, enhanced the expression of PRMT1 and the migration of donor and IPF fibroblasts. Interference with the expression or the activity of PRMT1 diminished the migration of the cells in response to IL-4. Strikingly, even though the incubation of donor and IPF fibroblasts with IL-4 did not affect their proliferation, depletion, but not blockage of PRMT1 activity suppressed cell growth.
  
  
  CONCLUSIONS
  PRMT1 can contribute to the development of pulmonary fibrosis by regulating fibroblast activities. Thus, interference with its expression and/or activity may provide a novel therapeutic option for patients with IPF.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany. Electronic address: dariusz.zakrzewicz@innere.med.uni-giessen.de.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Zakrzewicz
authors.affiliation: Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus Liebig University Giessen, Feulgenstrasse 10-12, 35385 Giessen, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Zakrzewicz
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Didiasova
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany.
authors.forename: Marek
authors.initials: M
authors.lastname: Korencak
authors.affiliation: Universities of Giessen and Marburg Lung Center, Aulweg 130, 35392 Giessen, Germany.
authors.forename: Djuro
authors.initials: D
authors.lastname: Kosanovic
authors.affiliation: Universities of Giessen and Marburg Lung Center, Aulweg 130, 35392 Giessen, Germany.
authors.forename: Ralph T
authors.initials: RT
authors.lastname: Schermuly
authors.affiliation: Department of Internal Medicine, Universities of Giessen and Marburg Lung Center, Klinikstrasse 33, 35392 Giessen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Markart
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Universities of Giessen and Marburg Lung Center, Friedrichstrasse 24, 35392 Giessen, Germany.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Wygrecka
keywords: ADMA; Arginine methylation; Fibroblasts; Interleukin-4; Migration; PRMT; Proliferation