Skip to main content
SLU publication database (SLUpub)

Research article2001Peer reviewedOpen access

Altered processing of fibronectin in mice lacking heparin: A role for heparin-dependent mast cell chymase in fibronectin degradation

Tchougounova, Elena; Forsberg, Erik; Angelborg, Gustaf; Kjellén, Lena; Pejler, Gunnar

Abstract

We have previously generated a mouse strain with a defect in its heparin biosynthesis by targeting the gene for N-deacetylase/N-sulfotransferase-2 (NDST-2). The NDST-2(-/-) mice show reduced levels of various mast cell mediators such as histamine and various heparin-binding mast cell proteases, including chymases, tryptases, and carboxypeptidase A In this work we have addressed the possible functional consequences of the lack of sulfated heparin. Peritoneal cells were harvested from normal and NDST-2(-/-) mice. After culturing the cells, conditioned media were collected and were subjected to SDS-polyacrylamide gel electrophoresis under reducing conditions. Several differences in the protein patterns were observed, including the presence of large amounts of a similar to 250-kDa protein in medium from NDST-2(-/-) mice that was absent in normal controls. Peptide microsequencing revealed identity of this protein with fibronectin. Western blot analysis showed the presence of fibronectin degradation products in cell cultures from normal mice, which were absent in cultures from NDST-2(-/-) animals. Further experiments showed that the degradation of fibronectin observed in cell cultures hom NDST-2(+/+) mice was catalyzed by mast cell chymase in a strongly heparin-dependent manner. This report thus indicates a biological function for chymase/heparin proteoglycan complexes in fibronectin turnover.

Published in

Journal of Biological Chemistry
2001, volume: 276, number: 6, pages: 3772-3777
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

SLU Authors

  • Tchougounova, Elena

    • Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences

  • Kjellén, Lena

    • Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences

  • Pejler, Gunnar

    • Department of Veterinary Medical Chemistry, Swedish University of Agricultural Sciences

Associated SLU-program

Future Animal Health and Welfare (until Jan 2017)

UKÄ Subject classification

Biochemistry
Biochemistry and Molecular Biology
Molecular Biology

Publication identifier

  • DOI: https://doi.org/10.1074/jbc.M008434200

Permanent link to this page (URI)

https://res.slu.se/id/publ/66607