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Involvement of platelet-derived growth factor receptor β in fibrosis through extracellular matrix protein production after ischemic stroke.
- Source :
-
Experimental neurology [Exp Neurol] 2015 Feb; Vol. 264, pp. 127-34. Date of Electronic Publication: 2014 Dec 13. - Publication Year :
- 2015
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Abstract
- Fibrosis is concomitant with repair processes following injuries in the central nervous system (CNS). Pericytes are considered as an origin of fibrosis-forming cells in the CNS. Here, we examined whether platelet-derived growth factor receptor β (PDGFRβ), a well-known indispensable molecule for migration, proliferation, and survival of pericytes, was involved in the production of extracellular matrix proteins, fibronectin and collagen type I, which is crucial for fibrosis after ischemic stroke. Immunohistochemistry demonstrated induction of PDGFRβ expression in vascular cells of peri-infarct areas at 3-7days in a mouse stroke model. The PDGFRβ-expressing cells extended from peri-infarct areas toward the ischemic core after day 7 while expressing fibronectin and collagen type I in the infarct areas. In contrast, desmin and α-smooth muscle actin, markers of pericytes, were only expressed in vascular cells. In PDGFRβ heterozygous knockout mice, the expression of fibronectin and collagen type I was attenuated at both mRNA and protein levels with an enlargement of the infarct volume after ischemic stroke compared with that in wild-type littermates. In cultured brain pericytes, the expression of PDGF-B, PDGFRβ, fibronectin, and collagen type I, but not desmin, was significantly increased by serum depletion (SD). The SD-induced upregulation of fibronectin and collagen type I was suppressed by SU11652, an inhibitor of PDGFRβ, while PDGF-B further increased the SD-induced upregulation. In conclusion, the expression level of PDGFRβ may be a crucial determinant of fibrosis after ischemic stroke. Moreover, PDGFRβ signaling participates in the production of fibronectin and collagen type I after ischemic stroke.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Brain cytology
Cells, Cultured
Disease Models, Animal
Enzyme Inhibitors pharmacology
Fibrosis
Gene Expression Regulation drug effects
Gene Expression Regulation physiology
Indoles pharmacology
Infarction, Middle Cerebral Artery blood
Mice
Mice, Inbred C57BL
Mice, Transgenic
Nerve Tissue Proteins metabolism
Pericytes metabolism
Pyrroles pharmacology
RNA, Messenger metabolism
Rats
Receptor, Platelet-Derived Growth Factor beta deficiency
Receptor, Platelet-Derived Growth Factor beta genetics
Time Factors
Extracellular Matrix Proteins metabolism
Gene Expression Regulation genetics
Infarction, Middle Cerebral Artery metabolism
Infarction, Middle Cerebral Artery pathology
Receptor, Platelet-Derived Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2430
- Volume :
- 264
- Database :
- MEDLINE
- Journal :
- Experimental neurology
- Publication Type :
- Academic Journal
- Accession number :
- 25510317
- Full Text :
- https://doi.org/10.1016/j.expneurol.2014.12.007