Proliferation of cultured mouse choroid plexus epithelial cells.

Proliferation of cultured mouse choroid plexus epithelial cells.
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DOI:
10.1371/journal.pone.0121738
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Monuki ES
Monuki ES
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Barkho BZ;Monuki ES

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脉络丛上皮是一种位于脑室的多功能组织。CHP上皮的主要功能是产生脑脊液(CSF),用于沐浴和滋养中枢神经系统(CNS)。除了脑脊液外,CHP上皮细胞(CPECs)还产生和分泌许多神经营养因子,支持脑内环境的稳定,如成年海马神经发生。因此,CPEC的损伤和功能障碍被认为会加速和加剧多种疾病的表型,CPEC的再生将成为治疗这些疾病的潜在途径。然而,以前的报告表明,CPEC很少分裂,尽管这一点尚未被广泛研究,以应对外部因素。利用细胞周期报告小鼠系和活细胞成像,我们确定划痕损伤和生长因子胰岛素样生长因子1(IGF-1)和表皮生长因子(EGF)是促进CPEC体外扩张的外在信号。此外,我们发现IGF-1和EGF处理增强了划痕损伤诱导的增殖。最后,我们建立了全组织外植体培养,观察到IGF-1和EGF促进完整的CHP上皮内CPEC的分裂。我们的结论是,尽管CPEC的周转率通常很低,但它们会对外界刺激(如损伤和/或生长因子)做出反应,这为脑损伤或神经变性后增强CHP功能提供了潜在的途径。
The choroid plexus (ChP) epithelium is a multifunctional tissue found in the ventricles of the brain. The major function of the ChP epithelium is to produce cerebrospinal fluid (CSF) that bathes and nourishes the central nervous system (CNS). In addition to the CSF, ChP epithelial cells (CPECs) produce and secrete numerous neurotrophic factors that support brain homeostasis, such as adult hippocampal neurogenesis. Accordingly, damage and dysfunction to CPECs are thought to accelerate and intensify multiple disease phenotypes, and CPEC regeneration would represent a potential therapeutic approach for these diseases. However, previous reports suggest that CPECs rarely divide, although this has not been extensively studied in response to extrinsic factors. Utilizing a cell-cycle reporter mouse line and live cell imaging, we identified scratch injury and the growth factors insulin-like growth factor 1 (IGF-1) and epidermal growth factor (EGF) as extrinsic cues that promote increased CPEC expansion in vitro. Furthermore, we found that IGF-1 and EGF treatment enhances scratch injury-induced proliferation. Finally, we established whole tissue explant cultures and observed that IGF-1 and EGF promote CPEC division within the intact ChP epithelium. We conclude that although CPECs normally have a slow turnover rate, they expand in response to external stimuli such as injury and/or growth factors, which provides a potential avenue for enhancing ChP function after brain injury or neurodegeneration.
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