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Characterization of fibroblast phenotypes in human airway remodeling

Larsen, Kristoffer LU (2005)
Abstract
Wound healing that precedes scar formation may be unbalanced under pathological conditions leading to structural changes of the tissue. At the moment, the mechanisms behind this unbalance are unclear. When these changes occur in internal organs such as the lung, they may result in organ dysfunction with fatal consequences for the patient. This phenomenon is defined as airway remodeling, and occurs in several pulmonary disorders such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and systemic sclerosis (SSc). Airway remodeling is characterized by a deposition of extracelullar matrix (ECM) components such as collagens, fibronectins, and proteoglycans.



It is generally accepted... (More)
Wound healing that precedes scar formation may be unbalanced under pathological conditions leading to structural changes of the tissue. At the moment, the mechanisms behind this unbalance are unclear. When these changes occur in internal organs such as the lung, they may result in organ dysfunction with fatal consequences for the patient. This phenomenon is defined as airway remodeling, and occurs in several pulmonary disorders such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and systemic sclerosis (SSc). Airway remodeling is characterized by a deposition of extracelullar matrix (ECM) components such as collagens, fibronectins, and proteoglycans.



It is generally accepted that activated fibroblasts play a key role in airway remodeling due to their ability to regulate the ECM turnover, which include the production and breakdown of connective tissue. When fibroblasts are activated they acquire a myofibroblast phenotype that is characterized by an increased production of ECM and contractility. Myofibroblasts are considered important target cells when studying airway remodeling and further characterization of these cells may lead to improved insights into the mechanisms behind this process. This is important since a majority of the therapies for these disorders are limited towards inflammatory response rather than tissue remodeling.



This thesis was aimed to characterize myofibroblast phenotypes and to elucidate the origin of these cells in airway remodeling, focused on tissue mainly derived from patients with mild asthma. To identify potential markers involved in disease mechanisms, methods used to study proteoglycan profiles and protein expression pattern (Proteomics) have been utilized. These topics, including the basics of airway remodeling, will be reviewed in the following sections. (Less)
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author
supervisor
opponent
  • MD, PhD Harrison, Kim, University of Swansea, Wales, UK
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Medicine (human and vertebrates), Medicin (människa och djur), remodeling, General biomedical sciences, Biomedicinska vetenskaper (allmänt), fibrocytes, proteoglycans, Asthma, fibroblasts
pages
117 pages
publisher
Department of Experimental Medical Science, Lund Univeristy
defense location
GK-salen, BMC, Sölvegatan 19, Lund
defense date
2005-11-18 09:15:00
ISBN
91-85481-16-5
language
English
LU publication?
yes
additional info
id
f51f7e2c-6c57-41c6-a0e2-b628f0606ffa (old id 545559)
date added to LUP
2016-04-01 15:47:55
date last changed
2018-11-21 20:36:27
@phdthesis{f51f7e2c-6c57-41c6-a0e2-b628f0606ffa,
  abstract     = {{Wound healing that precedes scar formation may be unbalanced under pathological conditions leading to structural changes of the tissue. At the moment, the mechanisms behind this unbalance are unclear. When these changes occur in internal organs such as the lung, they may result in organ dysfunction with fatal consequences for the patient. This phenomenon is defined as airway remodeling, and occurs in several pulmonary disorders such as asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and systemic sclerosis (SSc). Airway remodeling is characterized by a deposition of extracelullar matrix (ECM) components such as collagens, fibronectins, and proteoglycans.<br/><br>
<br/><br>
It is generally accepted that activated fibroblasts play a key role in airway remodeling due to their ability to regulate the ECM turnover, which include the production and breakdown of connective tissue. When fibroblasts are activated they acquire a myofibroblast phenotype that is characterized by an increased production of ECM and contractility. Myofibroblasts are considered important target cells when studying airway remodeling and further characterization of these cells may lead to improved insights into the mechanisms behind this process. This is important since a majority of the therapies for these disorders are limited towards inflammatory response rather than tissue remodeling.<br/><br>
<br/><br>
This thesis was aimed to characterize myofibroblast phenotypes and to elucidate the origin of these cells in airway remodeling, focused on tissue mainly derived from patients with mild asthma. To identify potential markers involved in disease mechanisms, methods used to study proteoglycan profiles and protein expression pattern (Proteomics) have been utilized. These topics, including the basics of airway remodeling, will be reviewed in the following sections.}},
  author       = {{Larsen, Kristoffer}},
  isbn         = {{91-85481-16-5}},
  keywords     = {{Medicine (human and vertebrates); Medicin (människa och djur); remodeling; General biomedical sciences; Biomedicinska vetenskaper (allmänt); fibrocytes; proteoglycans; Asthma; fibroblasts}},
  language     = {{eng}},
  publisher    = {{Department of Experimental Medical Science, Lund Univeristy}},
  school       = {{Lund University}},
  title        = {{Characterization of fibroblast phenotypes in human airway remodeling}},
  year         = {{2005}},
}