| Differential expression and activity of matrix metalloproteinase-2 and -9 in the calreticulin deficient cells. | |
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MedLine Citation:
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PMID: 17412577 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Min Wu; Hamid Massaeli; Melanie Durston; Nasrin Mesaeli |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-03-06 |
Journal Detail:
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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:
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Created Date: 2007-07-27 Completed Date: 2007-12-21 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9432592 Medline TA: Matrix Biol Country: Germany |
Other Details:
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Languages: eng Pagination: 463-72 Citation Subset: IM |
Affiliation:
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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. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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antagonists & inhibitors 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 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:
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0/Androstadienes; 0/Calreticulin; 0/Flavonoids; 0/PD 98059; 0/Protein Kinase Inhibitors; 0/RNA, Messenger; 0/Tissue Inhibitor of Metalloproteinase-1; 11061-68-0/Insulin; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; 19545-26-7/wortmannin; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; 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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