Differential expression and activity of matrix metalloproteinase-2 and -9 in the calreticulin deficient cells

Min Wu, Hamid Massaeli, Melanie Durston, Nasrin Mesaeli

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Calreticulin is an endoplasmic reticulum protein important in cardiovascular development. Deletion of the calreticulin gene leads to defects in the heart and the formation of omphaloceal. These defects could both be due to changes in the extracellular matrix composition. Matrix metalloproteinases (MMP)-2 and MMP-9 are two of the MMPs which are essential for cardiovascular remodelling and development. Here, we tested the hypothesis that the defects observed in the heart and body wall of the calreticulin null embryos are due to alterations in MMP-2 and MMP-9 activity. Our results demonstrate that there is a significant decrease in the MMP-9 and increase in the MMP-2 activity and expression in the calreticulin deficient cells. We also showed that there is a significant increase in the expression level of membrane type-1 matrix metalloproteinase (MT1-MMP). In contrast, there was no change in the tissue inhibitor of matrix metalloproteinase (TIMP)-1 or -2 in the calreticulin deficient cells as compared to the wild type cells. Interestingly, the inhibition of the MEK kinase pathway using PD98059 attenuated the decrease in the MMP-9 mRNA with no effect on the MMP-2 mRNA level in the calreticulin deficient cells. Furthermore, PI3 kinase inhibitor decreased the expression of both the MMP-2 and MMP-9. This study is the first report on the role of calreticulin in regulating MMP activity.

Original languageEnglish
Pages (from-to)463-472
Number of pages10
JournalMatrix Biology
Volume26
Issue number6
DOIs
Publication statusPublished - Jul 2007

    Fingerprint

Keywords

  • Calreticulin
  • MEK
  • MMP-9
  • MT1-MMP
  • Matrix metalloproteinase-2
  • PI3 kinase

ASJC Scopus subject areas

  • Molecular Biology

Cite this