uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Heparanase cleavage of heparin modulates protease storage in mast cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. (Jin-ping Li/Ulf Lindahl)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
Cancer and Vascular Biology Research Center, Technion, Haifa, Israel.
Cancer and Vascular Biology Research Center, Technion, Haifa, Israel.
Show others and affiliations
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Overexpression of heparanase caused extensive degradation of heparan sulfate (HS), and elimination of heparanase resulted in non-degraded HS chains in mice. In this study, we have investigated the impact of heparanase in the processing of heparin and storage of proteases in mast cells. We used fetal skin mast cells (FSMCs) isolated from wild type (WT) embryos and embryos either overexpressing human heparanase (hpa-tg), or lacking heparanase (Hpse-KO). FSMCs from hpa-tg embryos produced substantially shorter heparin chains than did WT counterparts, whereas FSMCs from Hpse-KO embryos expressed longer chains than WT cells. Extensive fragmentation of heparin in hpa-tg FSMC caused losing of proteases in the cells; in contrast, increased storage of proteases was observed in Hpse-KO cells. These results provide the first in vivo evidence demonstrating that heparanase is responsible for processing of mast cell heparin. Control of heparin degradation by heparanase in mast cell may contribute to modulating protease storage in the cells.

Keyword [en]
heparin, heparanase, mast cell, protease
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Biochemistry
Identifiers
URN: urn:nbn:se:uu:diva-107201OAI: oai:DiVA.org:uu-107201DiVA: diva2:228295
Available from: 2009-07-28 Created: 2009-07-28 Last updated: 2010-01-14Bibliographically approved
In thesis
1. Structure and functions of heparan sulfate/heparin – Importance of glucuronyl C5-epimerase and heparanase
Open this publication in new window or tab >>Structure and functions of heparan sulfate/heparin – Importance of glucuronyl C5-epimerase and heparanase
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Heparan sulfate (HS) and heparin are linear polysaccharide chains covalently O-linked to serine residues within the core proteins, so called HS proteoglycans (PGs) or heparin PG. HSPGs are produced by almost all mammalian cells and known to play important roles in developmental processes, physiological and pathological conditions; whereas heparin PG is produced by mast cells and best known as an anticoagulant in clinic.

Biosynthesis of HS/heparin occurs in Golgi compartment and involves many enzymes, one of which is glucuronyl C5-epimerase (Hsepi) that catalyzes the conversion of D-glucuronic acid (GlcA) to L-iduronic acid (IdoA). Heparanase is an enzyme involved in metabolism of HS; it cleaves the linkage between GlcA and glucosamine residues in HS/heparin chains. Heparanase is expressed essentially by all cells and found up-regulated in many metastatic tumors.

This thesis focuses on the structure and functions of HS/heparin through studies on the implications of Hsepi and heparanase. My study demonstrated that the modification catalyzed by Hsepi is critical for HS-dependent function of growth factors, especially FGF2; heparanase is involved in regulation of HS biosynthesis and matrix metalloproteinases expression; moreover, my experimental data demonstrated the functions of heparin in mast cells, showing cleavage of heparin by heparanase contributes to modulation of protease storage in mast cells.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 46 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 470
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Biochemistry
Identifiers
urn:nbn:se:uu:diva-107202 (URN)978-91-554-7571-0 (ISBN)
Public defence
2009-09-11, C10:301, BMC, Husargatan 3, Uppsala, 09:00 (English)
Opponent
Supervisors
Available from: 2009-08-20 Created: 2009-07-28 Last updated: 2009-08-20Bibliographically approved

Open Access in DiVA

No full text

Authority records BETA

Jia, JuanZhang, XiaoLindahl, UlfLi, Jin-ping

Search in DiVA

By author/editor
Jia, JuanZhang, XiaoLindahl, UlfLi, Jin-ping
By organisation
Department of Medical Biochemistry and MicrobiologyDepartment of Public Health and Caring Sciences
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 535 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf