Document Detail


Differential expression and activity of matrix metalloproteinase-2 and -9 in the calreticulin deficient cells.
MedLine Citation:
PMID:  17412577     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Min Wu; Hamid Massaeli; Melanie Durston; Nasrin Mesaeli
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-03-06
Journal Detail:
Title:  Matrix biology : journal of the International Society for Matrix Biology     Volume:  26     ISSN:  0945-053X     ISO Abbreviation:  Matrix Biol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-27     Completed Date:  2007-12-21     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  9432592     Medline TA:  Matrix Biol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  463-72     Citation Subset:  IM    
Affiliation:
Division of Stroke and Vascular Disease, St. Boniface General Hospital Research Centre, Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
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MeSH Terms
Descriptor/Qualifier:
Androstadienes / pharmacology
Animals
Blotting, Western
Calreticulin / deficiency,  genetics*
Cell Line
Embryonic Structures / cytology,  enzymology,  metabolism
Fibroblasts / drug effects,  enzymology,  metabolism
Flavonoids / pharmacology
Gene Expression Profiling*
Gene Expression Regulation, Developmental / drug effects
Immunohistochemistry
Insulin / pharmacology
Matrix Metalloproteinase 14 / genetics,  metabolism
Matrix Metalloproteinase 2 / genetics*,  metabolism
Matrix Metalloproteinase 9 / genetics*,  metabolism
Mice
Mice, Knockout
Phosphatidylinositol 3-Kinases / antagonists & inhibitors
Protein Kinase Inhibitors / pharmacology
RNA, Messenger / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
Tissue Inhibitor of Metalloproteinase-1 / genetics,  metabolism
Tissue Inhibitor of Metalloproteinase-2 / genetics,  metabolism
Chemical
Reg. No./Substance:
0/2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; 0/Androstadienes; 0/Calreticulin; 0/Flavonoids; 0/Insulin; 0/Protein Kinase Inhibitors; 0/RNA, Messenger; 0/Tissue Inhibitor of Metalloproteinase-1; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; 19545-26-7/wortmannin; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 3.4.24.-/Mmp9 protein, mouse; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.24/Mmp2 protein, mouse; EC 3.4.24.35/Matrix Metalloproteinase 9; EC 3.4.24.80/Matrix Metalloproteinase 14

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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