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Tissue repair in lung disorders

Andersson Sjöland, Annika LU (2009) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2009:122.
Abstract
The remodeling phase of tissue repair in lung disorders such as idiopathic pulmonary disease, asthma, obliterative bronchiolitis, and after lung transplantation is not well understood. One of the key players in fibrosis is the fibroblast and its progenitor, the fibrocyte. The fibroblast is the main producer of extracellular matrix molecules such as collagen, versican, perlecan, biglycan, and decorin. Fibrocytes are recruited from the bone marrow to the site of injury. It is possible that the stromal cell-derived factor-1/CXCL12 builds up in a gradient to recruit CXCR4 expressing fibrocytes, at least in the case of idiopathic pulmonary fibrosis. Patients with obliterative bronchilitis have an enlarged vessel lumen and a larger endothelial... (More)
The remodeling phase of tissue repair in lung disorders such as idiopathic pulmonary disease, asthma, obliterative bronchiolitis, and after lung transplantation is not well understood. One of the key players in fibrosis is the fibroblast and its progenitor, the fibrocyte. The fibroblast is the main producer of extracellular matrix molecules such as collagen, versican, perlecan, biglycan, and decorin. Fibrocytes are recruited from the bone marrow to the site of injury. It is possible that the stromal cell-derived factor-1/CXCL12 builds up in a gradient to recruit CXCR4 expressing fibrocytes, at least in the case of idiopathic pulmonary fibrosis. Patients with obliterative bronchilitis have an enlarged vessel lumen and a larger endothelial layer area, which has been shown to be correlated to more fibrocytes in the tissue. A correlation was found between the numbers of fibrocytes identified in tissue and structural changes in the lung. In idiopathic pulmonary fibrosis, a correlation was found between numbers of fibrocytes and numbers of fibroblastic foci, and in patients with obliterative bronchiolitis there was a correlation between fibrocyte numbers and thickening of the alveolar parenchyma. Eventually the fibrocyte enters the tissue and can differentiate into a fibroblast.



Matrix production by fibroblasts in patients who have undergone lung transplantation and in asthmatic subjects involves both the central and the distal parts of the lung. In lung-transplanted patients, the production of proteoglycans in the distal part was found to be double that in the central part. Versican production was particularly elevated compared to controls. The production of proteoglycans was further correlated with proliferation rate. A common feature of fibroblasts in patients after lung transplantation and asthmatic subjects was that these cells proliferated more slowly than in control subjects. Distally-derived fibroblasts from asthmatic subjects produced more veriscan, were immobile, and had many protrusions. The distal parts of the lungs were also rich in collagen.



A better understanding of fibrocyte and fibroblast function will help us to characterise the mechanisms behind idiopathic pulmonary disease, asthma, obliterative bronchiolitis. This knowledge can then be applied to other types of fibrotic disorders. (Less)
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author
supervisor
opponent
  • Pejler, Gunnar, Uppsala Universitet
organization
publishing date
type
Thesis
publication status
published
subject
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2009:122
pages
80 pages
publisher
Lund University, Faculty of Medicine
defense location
Belfragesalen, D15, BMC, Lund
defense date
2009-12-11 09:00
ISSN
1652-8220
ISBN
978-91-86443-11-5
language
English
LU publication?
yes
id
62c14d92-a2af-4f2c-8f7a-9a7954239c4f (old id 1503898)
date added to LUP
2009-11-20 09:47:58
date last changed
2016-09-19 08:44:46
@phdthesis{62c14d92-a2af-4f2c-8f7a-9a7954239c4f,
  abstract     = {The remodeling phase of tissue repair in lung disorders such as idiopathic pulmonary disease, asthma, obliterative bronchiolitis, and after lung transplantation is not well understood. One of the key players in fibrosis is the fibroblast and its progenitor, the fibrocyte. The fibroblast is the main producer of extracellular matrix molecules such as collagen, versican, perlecan, biglycan, and decorin. Fibrocytes are recruited from the bone marrow to the site of injury. It is possible that the stromal cell-derived factor-1/CXCL12 builds up in a gradient to recruit CXCR4 expressing fibrocytes, at least in the case of idiopathic pulmonary fibrosis. Patients with obliterative bronchilitis have an enlarged vessel lumen and a larger endothelial layer area, which has been shown to be correlated to more fibrocytes in the tissue. A correlation was found between the numbers of fibrocytes identified in tissue and structural changes in the lung. In idiopathic pulmonary fibrosis, a correlation was found between numbers of fibrocytes and numbers of fibroblastic foci, and in patients with obliterative bronchiolitis there was a correlation between fibrocyte numbers and thickening of the alveolar parenchyma. Eventually the fibrocyte enters the tissue and can differentiate into a fibroblast.<br/><br>
<br/><br>
Matrix production by fibroblasts in patients who have undergone lung transplantation and in asthmatic subjects involves both the central and the distal parts of the lung. In lung-transplanted patients, the production of proteoglycans in the distal part was found to be double that in the central part. Versican production was particularly elevated compared to controls. The production of proteoglycans was further correlated with proliferation rate. A common feature of fibroblasts in patients after lung transplantation and asthmatic subjects was that these cells proliferated more slowly than in control subjects. Distally-derived fibroblasts from asthmatic subjects produced more veriscan, were immobile, and had many protrusions. The distal parts of the lungs were also rich in collagen.<br/><br>
<br/><br>
A better understanding of fibrocyte and fibroblast function will help us to characterise the mechanisms behind idiopathic pulmonary disease, asthma, obliterative bronchiolitis. This knowledge can then be applied to other types of fibrotic disorders.},
  author       = {Andersson Sjöland, Annika},
  isbn         = {978-91-86443-11-5},
  issn         = {1652-8220},
  language     = {eng},
  pages        = {80},
  publisher    = {Lund University, Faculty of Medicine},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Tissue repair in lung disorders},
  volume       = {2009:122},
  year         = {2009},
}