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Functions of small leucine-rich repeat proteoglycans in connective tissues

Kalamajski, Sebastian LU (2008) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2008:30.
Abstract
Biological properties of connective tissues rely heavily on collagen and its use in formation of extracellular networks (matrices) in which cells can live and move. To regulate the process of collagen matrix assembly, the cells secrete small leucine-rich repeat proteoglycans (SLRPs) that bind to collagen and influence its fibril formation. In this manner, fibromodulin - one of the SLRPs - can alter intermolecular cross-linking of collagen, which has long-term implications for the structural integrity of the connective tissue. Since SLRPs can bind to collagen in via different domains, and are expressed in different tissues, their regulation of collagen matrices is fine-tuned for the physiological requirements. For example, decorin and... (More)
Biological properties of connective tissues rely heavily on collagen and its use in formation of extracellular networks (matrices) in which cells can live and move. To regulate the process of collagen matrix assembly, the cells secrete small leucine-rich repeat proteoglycans (SLRPs) that bind to collagen and influence its fibril formation. In this manner, fibromodulin - one of the SLRPs - can alter intermolecular cross-linking of collagen, which has long-term implications for the structural integrity of the connective tissue. Since SLRPs can bind to collagen in via different domains, and are expressed in different tissues, their regulation of collagen matrices is fine-tuned for the physiological requirements. For example, decorin and lumican interact with collagen using their central leucine-rich repeat domains, while fibromodulin makes use of its C-terminal domain. In addition, some SLRPs can inhibit each other's binding to collagen. These differences, together with the detailed knowledge on matrix protein interactions, can be useful to explain the development of connective tissues. In a longer time perspective, this knowledge could allow to manipulate fibrotic processes in pathological conditions like cancer or atherosclerosis - the two major causes of death in our society. The potential for such intervention is high, since fibromodulin is abundant in cancer stroma, raising its interstitial fluid pressure that hinders an efficient anti-cancer drug medication. Furthermore, fibromodulin is expressed in atherosclerotic plaques, regulating the growth of the fibrous cap and activity of smooth muscle cells. These observations validate further investigations into this field of connective tissue biology. (Less)
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author
supervisor
opponent
  • Prof. Paulsson, Mats, University of Cologne, Germany
organization
publishing date
type
Thesis
publication status
published
subject
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2008:30
pages
166 pages
publisher
Department of Experimental Medical Science, Lund Univeristy
defense location
Segerfalksalen, Wallenberg Neurocenter, BMC , Lund
defense date
2008-04-01 09:00
ISSN
1652-8220
ISBN
978-91-85897-83-4
language
English
LU publication?
yes
id
09151c39-79dd-4dca-ac5d-72fa96bc7947 (old id 1044892)
date added to LUP
2008-03-07 10:35:23
date last changed
2016-09-19 08:44:45
@phdthesis{09151c39-79dd-4dca-ac5d-72fa96bc7947,
  abstract     = {Biological properties of connective tissues rely heavily on collagen and its use in formation of extracellular networks (matrices) in which cells can live and move. To regulate the process of collagen matrix assembly, the cells secrete small leucine-rich repeat proteoglycans (SLRPs) that bind to collagen and influence its fibril formation. In this manner, fibromodulin - one of the SLRPs - can alter intermolecular cross-linking of collagen, which has long-term implications for the structural integrity of the connective tissue. Since SLRPs can bind to collagen in via different domains, and are expressed in different tissues, their regulation of collagen matrices is fine-tuned for the physiological requirements. For example, decorin and lumican interact with collagen using their central leucine-rich repeat domains, while fibromodulin makes use of its C-terminal domain. In addition, some SLRPs can inhibit each other's binding to collagen. These differences, together with the detailed knowledge on matrix protein interactions, can be useful to explain the development of connective tissues. In a longer time perspective, this knowledge could allow to manipulate fibrotic processes in pathological conditions like cancer or atherosclerosis - the two major causes of death in our society. The potential for such intervention is high, since fibromodulin is abundant in cancer stroma, raising its interstitial fluid pressure that hinders an efficient anti-cancer drug medication. Furthermore, fibromodulin is expressed in atherosclerotic plaques, regulating the growth of the fibrous cap and activity of smooth muscle cells. These observations validate further investigations into this field of connective tissue biology.},
  author       = {Kalamajski, Sebastian},
  isbn         = {978-91-85897-83-4},
  issn         = {1652-8220},
  language     = {eng},
  pages        = {166},
  publisher    = {Department of Experimental Medical Science, Lund Univeristy},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Functions of small leucine-rich repeat proteoglycans in connective tissues},
  volume       = {2008:30},
  year         = {2008},
}