FUNCTIONAL ANALYSIS OF PLATELET-DERIVED GROWTH FACTOR RECEPTOR-β IN NEURAL STEM/PROGENITOR CELLS

被引：17

作者：

Xu, G. ^{[1
,2
]}

Shen, J. ^{[1
,3
]}

Ishii, Y. ^{[1
]}

Fukuchi, M. ^{[4
]}

Dang, T. C. ^{[1
]}

Zheng, Y. ^{[1
]}

Hamashima, T. ^{[1
]}

Fujimori, T. ^{[5
]}

Tsuda, M. ^{[4
]}

Funa, K. ^{[6
]}

Sasahara, M. ^{[1
]}

机构：

[1] Toyama Univ, Grad Sch Med & Pharmaceut Sci, Dept Pathol, Toyama 9300152, Japan

[2] Inner Mongolia Peoples Hosp, Dept Pathol, Hohhot 010017, Inner Mongolia, Peoples R China

[3] Inner Mongolia Peoples Hosp, Dept Neurol, Hohhot 010017, Inner Mongolia, Peoples R China

[4] Toyama Univ, Grad Sch Med & Pharmaceut Sci, Toyama 9300152, Japan

[5] Natl Inst Basic Biol, Div Embryol, Okazaki, Aichi 4448787, Japan

[6] Univ Gothenburg, Sahlgrenska Acad, Sahlgrenska Canc Ctr, SE-40530 Gothenburg, Sweden

来源：

NEUROSCIENCE | 2013年 / 238卷

基金：

日本科学技术振兴机构;

关键词：

neural stem/progenitor cells; neurosphere; platelet-derived growth factor receptor; self-renewal; multipotency; NEUROTROPHIC FACTOR BDNF; STEM-CELLS; NEURONAL DIFFERENTIATION; STIMULATES PROLIFERATION; SUBVENTRICULAR ZONE; ADULT NEUROGENESIS; PDGF; BRAIN; EXPRESSION; KINASE;

D O I：

10.1016/j.neuroscience.2013.02.021

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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-beta-receptor-knockout (PDGFR-beta(-/-)) mice of postnatal day 1 (P1) and P28, and the roles of PDGFR-beta were examined in these cells. In PDGFR-beta-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-beta(-/-) 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-beta(-/-) 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-beta(-/-) as compared with P1 controls. Addition of BDNF rescued the number and diameter of secondary neurospheres in P1 PDGFR-beta(-/-) 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-beta 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-beta(-/-) NSPCs, whereas glial differentiation was comparable between the two genotypes. These results suggest that PDGFR-beta 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-beta signaling in these cells. Accordingly, the activation of PDGFR-beta in NSPCs may be a novel therapeutic strategy of neurological diseases. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

引用

页码：195 / 208

页数：14

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