| First Author | Makihara N | Year | 2015 |
| Journal | Exp Neurol | Volume | 264 |
| Pages | 127-34 | PubMed ID | 25510317 |
| Mgi Jnum | J:219766 | Mgi Id | MGI:5629663 |
| Doi | 10.1016/j.expneurol.2014.12.007 | Citation | Makihara N, et al. (2015) Involvement of platelet-derived growth factor receptor beta in fibrosis through extracellular matrix protein production after ischemic stroke. Exp Neurol 264:127-34 |
| abstractText | 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 beta (PDGFRbeta), 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 PDGFRbeta expression in vascular cells of peri-infarct areas at 3-7days in a mouse stroke model. The PDGFRbeta-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 alpha-smooth muscle actin, markers of pericytes, were only expressed in vascular cells. In PDGFRbeta 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, PDGFRbeta, 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 PDGFRbeta, while PDGF-B further increased the SD-induced upregulation. In conclusion, the expression level of PDGFRbeta may be a crucial determinant of fibrosis after ischemic stroke. Moreover, PDGFRbeta signaling participates in the production of fibronectin and collagen type I after ischemic stroke. |
