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Matrix Remodeling after Stroke: De Novo Expression of Matrix Proteins and Integrin Receptors
Author(s) -
ELLISON JULIE A.,
BARONE FRANK C.,
FEUERSTEIN GIORA Z.
Publication year - 1999
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1999.tb07996.x
Subject(s) - osteopontin , microglia , astrocyte , extracellular matrix , integrin , microbiology and biotechnology , glial scar , pathology , downregulation and upregulation , chemistry , matrix (chemical analysis) , biology , receptor , immunology , neuroscience , central nervous system , medicine , inflammation , biochemistry , gene , chromatography
Following an ischemic insult to the central nervous system a reorganization of cells and tissue takes place as the sorrounding cells attempt to limit the injury, repair the damage, and restore normal architecture of the brain. This tissue remodeling requires de novo synthesis of genes and proteins which enables cells to actively change their relationship with the existing extracellular matrix and with other cells to recognized the damage tissue. We have identified two key molecular components of the matrix remodeling process after focal ischemia: osteopontin (OPN) and its integrin receptor α v β 3 (α v β 3 ). OPN is initially expressed by activated macrophages and microglia in the periinfarct region (24–48 hr) and at later times (5–15 days) in the core infarct. After focal stroke the α v β 3 was upregulated by astrocytes in the periinfarct region. Spatial and temporal analyses demonstrated that at 5 days after injury the α v β 3 ‐positive astrocytes were at a distance from the osteopontin‐expressing macrophages; by 15 days the α v β 3 ‐expressing astrocytes were localized within an osteopontin‐rich matrix. In vitro OPN was shown to induce migration of astrocytes in a Boyden chamber system. These data suggest that OPN derived from microglia at the infarct border zone (and possible macrophages in the infarct core) may serve as an “astrokine” (suggested term for astrocyte chemoattractant) to organize the astrocyte scar after focal stroke. Our data demonstrate profound changes in brain matrix remodeling after focal ischemic stroke, including the systhesis and release of matrix proteins alien to the normal brain, the expresion of integrin receptors that ligate these proteins, and possibly a novel function for microglial‐derived OPN in astrocyte migration after focal ischemia that may drive glial activation, organization, and repair functions.