Elevated level of fibrinogen increases caveolae formation; Role of matrix metalloproteinase-9
| Autor: | Richard L. Benton, David Lominadze, Reeta Tyagi, Suresh C. Tyagi, Nino Muradashvili |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Caveolin 1 Biophysics Biology Fibrinogen Blood–brain barrier Caveolae Biochemistry Article Cell Line Mice medicine Animals Phosphorylation Gene knockout Mice Knockout Brain Endothelial Cells Membrane Proteins Tissue Inhibitor of Metalloproteinases Cell Biology General Medicine Molecular biology Immunohistochemistry Mice Inbred C57BL medicine.anatomical_structure Transcytosis Matrix Metalloproteinase 9 Cell culture Blood-Brain Barrier Carrier Proteins medicine.drug |
| Popis: | The role of the inflammatory agent fibrinogen (Fg) in increased pial venular permeability has been shown previously. It was suggested that an activation of matrix metalloproteinase-9 (MMP-9) is involved in Fg-induced enhanced transcytosis through endothelial cells. However, direct link between Fg, caveolae formation, and MMP-9 activity has never been shown. We hypothesized that at an elevated level, Fg enhances formation of functional caveolae through activation of MMP-9. Male wild-type (WT, C57BL/6J) or MMP-9 gene knockout (MMP9−/−) mice were infused with Fg (4 mg/ml, final blood concentration) or equal volume of phosphate buffered saline (PBS). After 2 hours, mice were sacrificed and brains were collected for immunohistochemical analyses. Mouse brain endothelial cells were treated with 4 mg/ml of Fg or PBS in the presence or absence of MMP-9 activity inhibitor, tissue inhibitor of metalloproteinases-4 (TIMP-4, 12 ng/ml). Formation of functional caveolae was assessed by confocal microscopy. Fg-induced increased formation of caveolae, which was defined by an increased co-localization of caveolin-1 (Cav-1) and plasmalemmal vesicle-associated protein-1 (PV-1) and was associated with an increased phosphorylation of Cav-1, was ameliorated in the presence of TIMP-4. These results suggest that at high levels, Fg enhances formation of functional caveolae that may involve Cav-1 signaling and MMP-9 activation. |
| Databáze: | OpenAIRE |
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