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A proteomic approach to mimic fibrosis disease evolvement by an in vitro cell line

Malmström, Johan LU ; Westergren-Thorsson, Gunilla LU and Marko-Varga, György LU (2001) In Electrophoresis 22(9). p.1776-1784
Abstract
Subepithelial fibrosis in asthma involves an increase in the thickening of the lamina reticularis and is due to increased deposition of collagen I, III and V, and fibronectin. The cause of the thickening of the reticular layer is not known in detail, however, it is proposed to be caused by bronchial myofibroblasts. The transformation of fibroblasts to myofibroblasts may be contributed by inflammatory cytokines. In this paper we have studied and compared in vivo tissue material with a human fibroblast target cell. A normal primary fetal fibroblast cell line and HFL-1 (human fibroblast lurg cells) were used as a comparison between fibroblasts from human central biopsies regarding morphology and cell proliferation. Both cell morphology and... (More)
Subepithelial fibrosis in asthma involves an increase in the thickening of the lamina reticularis and is due to increased deposition of collagen I, III and V, and fibronectin. The cause of the thickening of the reticular layer is not known in detail, however, it is proposed to be caused by bronchial myofibroblasts. The transformation of fibroblasts to myofibroblasts may be contributed by inflammatory cytokines. In this paper we have studied and compared in vivo tissue material with a human fibroblast target cell. A normal primary fetal fibroblast cell line and HFL-1 (human fibroblast lurg cells) were used as a comparison between fibroblasts from human central biopsies regarding morphology and cell proliferation. Both cell morphology and cell proliferation rate was similar between the different set of cell cultures. Furthermore, it could be concluded that fibroblasts cultures from patients with asthma were surrounded by more extracellular matrix molecules compared to the primary cell line HFL-1, which may mimic the in vivo situation during formation of fibrosis. We wanted to investigate if differential protein display by two-dimensional (2-D) gel electrophoresis and subsequent protein identification by matrix assisted laser desorption/ionization-time of flight (MALDI-TOF)-mass spectrometry could reveal proteins induced by cytokine stimulation that can be correlated to the transformation of normal human fetal lungs cells into a more myofibroblast like phenotype. After stimulation with transforming growth factor-beta (TGF-beta) several myofibroblast markers were found to be regulated. Especially cytoskeletal and cytoskeletal-associated proteins like actin isoforms and tropomyosin, proteins that are responsible for contraction as well as transportation of extra cellular matrix proteins, which are overproduced in the formation of fibrosis. These results indicate that TGF-beta, which is increased in a fibrotic process, participates in the transformation of fibroblasts to myofibroblasts. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Fibroblasts, Two-dimensional gel, Fibrosis, Lung and transforming growth factor-
in
Electrophoresis
volume
22
issue
9
pages
1776 - 1784
publisher
John Wiley & Sons
external identifiers
  • wos:000169298900019
  • scopus:66249143091
ISSN
0173-0835
DOI
10.1002/1522-2683(200105)22:9<1776::AID-ELPS1776>3.0.CO;2-H
language
English
LU publication?
yes
id
ca01978b-5693-4ac7-88b1-1e397a2e3d73 (old id 1119153)
date added to LUP
2008-07-04 13:49:04
date last changed
2018-01-07 05:57:00
@article{ca01978b-5693-4ac7-88b1-1e397a2e3d73,
  abstract     = {Subepithelial fibrosis in asthma involves an increase in the thickening of the lamina reticularis and is due to increased deposition of collagen I, III and V, and fibronectin. The cause of the thickening of the reticular layer is not known in detail, however, it is proposed to be caused by bronchial myofibroblasts. The transformation of fibroblasts to myofibroblasts may be contributed by inflammatory cytokines. In this paper we have studied and compared in vivo tissue material with a human fibroblast target cell. A normal primary fetal fibroblast cell line and HFL-1 (human fibroblast lurg cells) were used as a comparison between fibroblasts from human central biopsies regarding morphology and cell proliferation. Both cell morphology and cell proliferation rate was similar between the different set of cell cultures. Furthermore, it could be concluded that fibroblasts cultures from patients with asthma were surrounded by more extracellular matrix molecules compared to the primary cell line HFL-1, which may mimic the in vivo situation during formation of fibrosis. We wanted to investigate if differential protein display by two-dimensional (2-D) gel electrophoresis and subsequent protein identification by matrix assisted laser desorption/ionization-time of flight (MALDI-TOF)-mass spectrometry could reveal proteins induced by cytokine stimulation that can be correlated to the transformation of normal human fetal lungs cells into a more myofibroblast like phenotype. After stimulation with transforming growth factor-beta (TGF-beta) several myofibroblast markers were found to be regulated. Especially cytoskeletal and cytoskeletal-associated proteins like actin isoforms and tropomyosin, proteins that are responsible for contraction as well as transportation of extra cellular matrix proteins, which are overproduced in the formation of fibrosis. These results indicate that TGF-beta, which is increased in a fibrotic process, participates in the transformation of fibroblasts to myofibroblasts.},
  author       = {Malmström, Johan and Westergren-Thorsson, Gunilla and Marko-Varga, György},
  issn         = {0173-0835},
  keyword      = {Fibroblasts,Two-dimensional gel,Fibrosis,Lung and transforming growth factor-},
  language     = {eng},
  number       = {9},
  pages        = {1776--1784},
  publisher    = {John Wiley & Sons},
  series       = {Electrophoresis},
  title        = {A proteomic approach to mimic fibrosis disease evolvement by an in vitro cell line},
  url          = {http://dx.doi.org/10.1002/1522-2683(200105)22:9<1776::AID-ELPS1776>3.0.CO;2-H},
  volume       = {22},
  year         = {2001},
}