Biglycan as a modulator of fibrous connective tissue

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Fibrous connective tissue contains fibroblasts distributed in a complex network of extracellular matrix molecules, such as proteoglycans. The small proteoglycans biglycan and decorin are composed of a protein core substituted with two and one glycosaminoglycan (GAG) chain, respectively. Proteoglycan metabolism is regulated differently during several processes including inflammation and wound healing. Proinflammatory cytokines, such as TNF-a and IL-1b, can affect matrix composition by increasing biglycan, versican and hyaluronan, and decreasing decorin and collagen. This results in a more loosely associated connective tissue that enhances the infiltration of inflammatory cells. Moreover, TNF-a can bind to both biglycan and decorin. In the inflammatory process, this may be of utmost importance since biglycan and decorin are located and regulated differently. The pericellular location of biglycan can enhance the binding of TNF-a to its cell surface receptors, while decorin, located in the extracellular matrix, may function as a storage depot. Besides the predominant form of biglycan, different isoforms can be secreted that possess a smaller core protein and greater diversity in the structure and length of their GAG chains. This variation in the structure of biglycan may alter its ability to bind cytokines as well as other matrix molecules potentially resulting in changes in the connective tissue formation. Biglycan and decorin also have important functions in the tissue repair process where they induce fibroblast cytoskeletal changes. These include morphological changes to a longer, stretched cell shape, formation of stress fibres and focal adhesions. These may be caused by an activation of the Rho GTPases, RhoA and Rac1, followed by an increase in migration. In summary, our results demonstrate that biglycan and decorin affect fibroblast activity and that they have a role both in physiological and pathological processes where the extracellular matrix is continuously being remodelled.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • biglycan/decorin/fibroblast/interleukin-1beta/migration/proteoglycan/structure/tumour necrosis factor-alpha, Medicine (human and vertebrates), Medicin (människa och djur)
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
  • [unknown], [unknown], Supervisor, External person
Award date2002 Sep 28
Publisher
  • Ellen Tufvesson, BMC, C13, Lund University, 221 84 Lund,
Print ISBNs91-628-5328-7
Publication statusPublished - 2002
Publication categoryResearch

Bibliographic note

Defence details Date: 2002-09-28 Time: 10:15 Place: N/A External reviewer(s) Name: Laurent, Geoffrey Title: [unknown] Affiliation: University College London --- Article: I. Alteration of proteoglycan synthesis in human lung fibroblasts induced by IL-1beta and TNF-alpha.Ellen Tufvesson and Gunilla Westergren-Thorsson, (2000). J Cell Biochem 77, 298-309. Article: II. Biglycan isoforms and differences in polysaccharide substitution and core protein in human lung fibroblasts.Ellen Tufvesson, Johan Malmström, György Marko-Varga and Gunilla Westergren-Thorsson, (2002). Eur J Biochem 269, 3688-3696. Article: III. TNF-alpha interacts with biglycan and decorin.Ellen Tufvesson and Gunilla Westergren-Thorsson. Submitted to FEBS Lett. Article: IV. Biglycan and decorin induce morphological and cytoskeletal changes involving signalling by the small GTPases RhoA and Rac1 in lung fibroblasts.Ellen Tufvesson and Gunilla Westergren-Thorsson. In manuscript. The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Cell and Matrix Biology (LUR000002), Respiratory Medicine and Allergology (013230111)