TY - JOUR
T1 - Functional analysis of platelet-derived growth factor receptor-β in neural stem/progenitor cells
AU - Xu, G.
AU - Shen, J.
AU - Ishii, Y.
AU - Fukuchi, M.
AU - Dang, T. C.
AU - Zheng, Y.
AU - Hamashima, T.
AU - Fujimori, T.
AU - Tsuda, M.
AU - Funa, K.
AU - Sasahara, M.
N1 - Funding Information:
We thank Yoichi Kurashige, Takako Matsushima and Miwa Fujikawa for technical assistance, and Masako Tonami for preparing the manuscript (University of Toyama, Japan). This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan , and Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST; Grants 23590444 , 20590381 and 20390108 ).
PY - 2013/5/15
Y1 - 2013/5/15
N2 - Activation of neural stem/progenitor cells (NSPCs) is a potential therapeutic strategy of neurological disorders. In this study, NSPCs of subventricular zone were isolated and cultured from platelet-derived growth factor-β-receptor-knockout (PDGFR-β-/-) mice of postnatal day 1 (P1) and P28, and the roles of PDGFR-β were examined in these cells. In PDGFR-β-preserving control NSPCs, stem cell activities, such as numbers and diameters of secondary neurospheres, cell proliferation and survival rates, were significantly higher in P1 NSPCs than those in P28 NSPCs. In PDGFR-β-/- NSPCs, most of these parameters were decreased as compared with age-matched controls. Among them, the decrease of secondary neurosphere formation was most striking in P1 and P28 PDGFR-β-/- NSPCs and in P28 control NSPCs as compared with P1 control NSPCs. PCR-array and following quantitative real-time PCR (qRT-PCR) analyses demonstrated that expressions of fibroblast growth factor-2 (FGF2) and exons IV-IX of brain-derived neurotrophic factor (BDNF) were decreased, and noggin was increased in P1 PDGFR-β-/- as compared with P1 controls. Addition of BDNF rescued the number and diameter of secondary neurospheres in P1 PDGFR-β-/- NSPCs to similar levels as controls. The expressions of PDGFs and PDGFRs in control NSPCs were increased along with the differentiation-induction, where phosphorylated PDGFR-β was co-localized with neuronal and astrocyte differentiation markers. In controls, the neuronal differentiation was decreased, and the glial differentiation was increased from P1 to P28 NSPCs. Compared with P1 controls, neuronal differentiation was reduced in P1 PDGFR-β-/- NSPCs, whereas glial differentiation was comparable between the two genotypes. These results suggest that PDGFR-β signaling is important for the self-renewal and multipotency of NSPCs, particularly in neonatal NSPCs. BDNF, FGF2, and noggin may be involved in the effects of PDGFR-β signaling in these cells. Accordingly, the activation of PDGFR-β in NSPCs may be a novel therapeutic strategy of neurological diseases.
AB - Activation of neural stem/progenitor cells (NSPCs) is a potential therapeutic strategy of neurological disorders. In this study, NSPCs of subventricular zone were isolated and cultured from platelet-derived growth factor-β-receptor-knockout (PDGFR-β-/-) mice of postnatal day 1 (P1) and P28, and the roles of PDGFR-β were examined in these cells. In PDGFR-β-preserving control NSPCs, stem cell activities, such as numbers and diameters of secondary neurospheres, cell proliferation and survival rates, were significantly higher in P1 NSPCs than those in P28 NSPCs. In PDGFR-β-/- NSPCs, most of these parameters were decreased as compared with age-matched controls. Among them, the decrease of secondary neurosphere formation was most striking in P1 and P28 PDGFR-β-/- NSPCs and in P28 control NSPCs as compared with P1 control NSPCs. PCR-array and following quantitative real-time PCR (qRT-PCR) analyses demonstrated that expressions of fibroblast growth factor-2 (FGF2) and exons IV-IX of brain-derived neurotrophic factor (BDNF) were decreased, and noggin was increased in P1 PDGFR-β-/- as compared with P1 controls. Addition of BDNF rescued the number and diameter of secondary neurospheres in P1 PDGFR-β-/- NSPCs to similar levels as controls. The expressions of PDGFs and PDGFRs in control NSPCs were increased along with the differentiation-induction, where phosphorylated PDGFR-β was co-localized with neuronal and astrocyte differentiation markers. In controls, the neuronal differentiation was decreased, and the glial differentiation was increased from P1 to P28 NSPCs. Compared with P1 controls, neuronal differentiation was reduced in P1 PDGFR-β-/- NSPCs, whereas glial differentiation was comparable between the two genotypes. These results suggest that PDGFR-β signaling is important for the self-renewal and multipotency of NSPCs, particularly in neonatal NSPCs. BDNF, FGF2, and noggin may be involved in the effects of PDGFR-β signaling in these cells. Accordingly, the activation of PDGFR-β in NSPCs may be a novel therapeutic strategy of neurological diseases.
KW - Multipotency
KW - Neural stem/progenitor cells
KW - Neurosphere
KW - Platelet-derived growth factor receptor
KW - Self-renewal
UR - http://www.scopus.com/inward/record.url?scp=84875586083&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2013.02.021
DO - 10.1016/j.neuroscience.2013.02.021
M3 - 学術論文
C2 - 23454370
AN - SCOPUS:84875586083
SN - 0306-4522
VL - 238
SP - 195
EP - 208
JO - Neuroscience
JF - Neuroscience
ER -