Notch1-STAT3-ETBR signaling in brain injury and cancer.
Notch1-STAT3-ETBR signaling in brain injury and cancer.
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DOI：
10.1016/j.cyto.2015.08.259
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发表时间：
2016-04
期刊：
影响因子：
3.8
通讯作者：
Spees JL
中科院分区：
文献类型：
--
作者：
LeComte MD;Spees JL
基于它们与CNS损伤或疾病部位的相对距离和损伤的严重程度，星形胶质细胞和其他神经胶质细胞特征性地变得“反应性”。反应性星形胶质细胞在表型上不同于存在于正常健康组织中的成熟原生质或纤维星形胶质细胞。在反应性星形胶质细胞增生的过程中，成熟的星形胶质细胞经历基因和蛋白质表达的急剧变化，从而引起形态（肥大）和细胞周期状态的变化（图1）。活化的反应性星形胶质细胞靠近受损/垂死的细胞执行关键功能，包括神经保护、血脑屏障（BBB）的保存/重建、免疫细胞应答的调节和神经胶质瘢痕形成[1]。重要的是，控制反应性星形胶质细胞增生的信号网络的机制理解和映射具有很大的潜力，以阐明治疗靶点，并为开发新的治疗方法提供信息，以促进CNS损伤或疾病患者的恢复和改善结局。成纤维细胞生长因子（FGF）和内皮素（ET-1）。已知触发反应性星形胶质细胞增生的其他细胞因子/生长因子、分子和病症包括（但不限于）：IL-1、IL-6、IL-10、LIF、CNTF、BMP、TGF-β、TNF-α、INF-γ、脂多糖、谷氨酸、三磷酸腺苷、一氧化氮、活性氧以及组织缺血期间的缺氧和葡萄糖剥夺[1]。尽管在CNS损伤期间释放或产生的许多信号已显示刺激培养物中的反应性星形胶质细胞，但调节体内反应性星形胶质细胞增殖和功能的复杂信号传导网络仍然知之甚少。
Based on their relative distance from sites of CNS injury or disease and the severity of insult, astrocytes and other glial cells characteristically become “reactive”. Reactive astrocytes are phenotypically different from mature protoplasmic or fibrous astrocytes that reside in normal, healthy tissue. During the process of reactive astrogliosis, mature astrocytes undergo dramatic changes in gene and protein expression that beget changes in morphology (hypertrophy) and cell cycle status (Fig 1). Proliferating reactive astrocytes in close proximity to damaged/dying cells carry out key functions that include neuroprotection, preservation/re-establishment of the blood-brain barrier (BBB), regulation of immune cell responses, and glial scar formation [1]. Importantly, mechanistic understanding and mapping of the signaling network that controls reactive astrogliosis has great potential to elucidate therapeutic targets and inform the development of new treatments to promote recovery and improve outcomes in patients with CNS injury or disease.Multiple proteins/peptides commonly released during CNS injury have been shown to stimulate reactive astrocyte proliferation such as epidermal growth factor (EGF), fibroblast growth factor (FGF), and endothelin (ET-1). Other cytokines/growth factors, molecules, and conditions known to trigger reactive astrogliosis include (but are not limited to): IL-1, IL-6, IL-10, LIF, CNTF, BMP, TGF-β, TNF-α, INF-γ, lipopolysaccharide, glutamate, adenosine triphosphate, nitric oxide, reactive oxygen species, and hypoxia and glucose deprivation during tissue ischemia [1]. Although numerous signals released or produced during CNS injury have been shown to stimulate reactive astrocytes in culture, the complex signaling network that regulates reactive astrocyte proliferation and function (s) in vivo remains poorly understood.