红参诱导的星形细胞HIF-1α：生理性视网膜和脑神经干细胞分化神经红蛋白的关键调节因子

IF 6.8 2区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Ginseng Research Pub Date : 2024-12-31 DOI:10.1016/j.jgr.2024.12.008

Sunhong Moon , Jinseo Park , Sueun Kim , Minsu Kim , Hui Su Jeon , Hyungsu Kim , Young-Myeong Kim , Ji-Yoon Kim , Yoon Kyung Choi

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引用次数: 0

摘要

神经元中的神经球蛋白（Ngb）和生长相关蛋白（GAP） 43与轴突再生有关。高丽红参提取物（KRGE）增强胶质纤维酸性蛋白（GFAP）阳性星形胶质细胞和缺氧诱导因子-1α (HIF-1α)蛋白的活性。然而，krge处理的正常大脑和视网膜中，神经干细胞（NSC）分化和星形细胞HIF-1α之间的串扰尚不清楚。我们研究了krge处理的星形细胞HIF-1α是否能促进NSC分化，增加Ngb和GAP43的成熟神经元表达。方法用Ngb检测krge给药后小鼠脑或视网膜组织中神经元核（NeuN）或微管相关蛋白2 （MAP2）等成熟神经元标志物。评价KRGE直接治疗NSCs或星形胶质细胞的Ngb水平。将krge处理的星形胶质细胞条件培养基（ACM）转移到NSCs中，通过小干扰RNA转染（si-HIF-1α）降低星形胶质细胞中的HIF-1α水平。si-HIF-1α-ACM结合KRGE进行NSC分化试验。结果与水给药小鼠相比，skrge给药小鼠脑内Ngb与NeuN、视网膜内MAP2及NSC标记物Nestin的共表达显著增强。KRGE处理并未增加Ngb水平，但刺激星形胶质细胞分泌影响NSCs向成熟神经元和星形胶质细胞分化的因子。krge处理的小鼠视网膜显示GFAP-和HIF-1α双阳性细胞。与si- hif -1α-转染的KRGE-ACM共处理可阻断KRGE-ACM诱导的NSC向星形胶质细胞或表达ngb的神经元的分化。结论krge刺激星形胶质细胞HIF-1α，调节NSC向表达Ngb的成熟神经元分化，从而通过增强生理视网膜和脑内NSC -星形胶质细胞串音促进再生。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Korean Red Ginseng-induced astrocytic HIF-1α: A key regulator of neuroglobin derived from neural stem cell differentiation in physiologic retina and brain

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Korean Red Ginseng-induced astrocytic HIF-1α: A key regulator of neuroglobin derived from neural stem cell differentiation in physiologic retina and brain

Background

Neuroglobin (Ngb) and growth-associated protein (GAP) 43 in neurons are associated with axonal regeneration. Korean Red Ginseng Extract (KRGE) enhances glial fibrillary acidic protein (GFAP)-positive astrocytes and hypoxia-inducible factor-1α (HIF-1α) protein activation in normoxic astrocytes. However, crosstalk between neural stem cell (NSC) differentiation and astrocytic HIF-1α in the KRGE-treated normoxic brain and retina remains unclear. We investigated whether KRGE-treated astrocytic HIF-1α can enhance NSC differentiation and increase the mature neurons expressing Ngb and GAP43.

Methods

Mature neuronal markers such as neuronal nuclei (NeuN) or microtubule-associated protein 2 (MAP2) were tested with Ngb in the mouse brain or retinal tissues post-KRGE administration. Direct KRGE treatment of NSCs or astrocytes was evaluated for Ngb levels. The KRGE-treated astrocyte conditioned media (ACM) were transferred to NSCs and HIF-1α levels were reduced using small interfering RNA transfection (si-HIF-1α) in astrocytes. si-HIF-1α-ACM with KRGE was tested for NSC differentiation.

Results

KRGE-administered mice showed significantly enhanced co-expression of Ngb with NeuN in the brain and MAP2 in the retina, along with the NSC marker Nestin, than water-administered mice. The KRGE treatment did not increase Ngb levels in NSCs, but stimulated astrocytes to secrete factors affecting NSCs’ differentiate into mature neurons and astrocytes. The KRGE-treated mouse retinas showed GFAP- and HIF-1α double-positive cells. Co-treatment with si-HIF-1α-transfected KRGE–ACM blocked KRGE–ACM-induced NSC differentiation into astrocytes or Ngb-expressing neurons.

Conclusion

KRGE stimulates astrocytic HIF-1α, which regulates NSC differentiation into mature neurons expressing Ngb, thereby promoting regeneration by enhancing NSC–astrocyte crosstalk in the physiological retina and brain.

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来源期刊

Journal of Ginseng Research CHEMISTRY, MEDICINAL-INTEGRATIVE & COMPLEMENTARY MEDICINE

CiteScore

11.40

自引率

9.50%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Journal of Ginseng Research (JGR) is an official, open access journal of the Korean Society of Ginseng and is the only international journal publishing scholarly reports on ginseng research in the world. The journal is a bimonthly peer-reviewed publication featuring high-quality studies related to basic, pre-clinical, and clinical researches on ginseng to reflect recent progresses in ginseng research. JGR publishes papers, either experimental or theoretical, that advance our understanding of ginseng science, including plant sciences, biology, chemistry, pharmacology, toxicology, pharmacokinetics, veterinary medicine, biochemistry, manufacture, and clinical study of ginseng since 1976. It also includes the new paradigm of integrative research, covering alternative medicinal approaches. Article types considered for publication include review articles, original research articles, and brief reports. JGR helps researchers to understand mechanisms for traditional efficacy of ginseng and to put their clinical evidence together. It provides balanced information on basic science and clinical applications to researchers, manufacturers, practitioners, teachers, scholars, and medical doctors.