Notch信号在表皮及皮肤疾病中的研究进展

Notch信号通路是人体重要信号通路,其信号分子在机体内的各个器官中均有表达,其作用涉及细胞周期调节、细胞增殖及凋亡。皮肤作为人体重要的器官,在人的生命活动中一直不断的更新。据近期一系列研究报道,在包括角质形成细胞等多种表皮细胞的表面,Notch及其配体均有大量表达,且特异性的Notch信号活化在维持皮肤细胞自身更新及分化过程中起重要作用。本文就Notch信号在表皮及皮肤疾病中的研究进展和现状综述如下。     

姜黄素对前列腺癌PC3细胞生长及Notchl信号的作用

研究表明Notch信号通路在器官、细胞发育及肿瘤发生等病理生理过程中起重要作用[1].Notch信号通路尤其是Notch1蛋白的表达与前列腺的发育和肿瘤转化密切相关[2-3].我们通过观察姜黄素对PC-3细胞体外增殖、凋亡及Notch1和配体Jagged1表达的影响,探讨其对雄激素非依赖性前列腺癌细胞的作用.     

Notch信号通路参与免疫炎症反应的研究进展

背景 Notch信号通路是影响细胞命运的重要通路之一,在细胞分化、增殖、存活和发育中起关键作用.近年来研究表明,Notch信号还参与许多病理生理过程和多种疾病的发生、发展.目的 研究Notch信号通路在免疫炎症反应之间的作用,寻求新的免疫炎症调控靶点.内容 主要综述了Notch信号通路与免疫炎症反应的密切关系,以及对炎症性疾病的调控.趋向 Notch信号在各种炎症性疾病包括全身炎症反应综合征(systemic inflammatory response syndrome,SIRS)及脓毒症中的具体机制仍不清楚,还需更深入的研究.     

Notch信号通路在骨髓间充质干细胞及骨代谢疾病中的功能研究进展

骨髓间充质干细胞是存在于骨髓基质中的一种多能干细胞,具有多向分化的潜能,其天然再生能力对骨骼的生长代谢和骨转换起着至关重要的作用。Notch信号通路是一条在进化中高度保守的信号转导通路,与骨髓间充质干细胞的增殖、分化与凋亡密切相关,影响人体骨骼发育,也是多种骨代谢疾病的重要调节通路。以往对Notch信号通路的研究主要集中在神经干细胞,对骨髓间充质干细胞的研究较少。本文通过查阅文献,阐述不同的影响因素介导Notch信号通路对骨髓间充质干细胞分化的调节,并总结了Notch信号通路在骨代谢疾病如Alagille综合征、Adams Oliver综合征、脊椎肋骨发育不良、HajduCheney综合征、骨折愈合中的研究近况。     

运动对软骨代谢影响的研究进展

骨关节炎是临床常见病,也是难治疾病之一,因其软骨损伤后较难修复。不同的信号通路对软骨代谢具有调节作用,笔者列举了软骨代谢中3条经典通路Notch、Wnt及MAPK信号通路,并阐述分析了Notch、Wnt及MAPK信号通路对不同时期软骨细胞代谢,以及软骨受损时软骨代谢的影响。同时,总结了运动对受损关节软骨的影响及作用机制,为运动治疗骨关节炎提供一定理论参考。     

Notch信号通路与肝癌细胞凋亡关系的研究进展

肝癌细胞中Notch信号通路异常传导,因肝癌细胞异质性,Notch信号通路既可抑制肝癌细胞凋亡,又可促进肝癌细胞凋亡。Notch信号通路通过与其他细胞信号通路的“串扰”,或直接影响内外细胞凋亡途径,调控肝癌细胞凋亡。本文综述了上调或下调Notch信号通路促进肝癌细胞凋亡的最新研究结果,回顾了Notch信号通路在肝癌细胞凋亡途径中的不同作用机制,为肝癌的Notch信号通路靶向治疗提供理论支持。     

脓毒症肺损伤相关信号转导通路研究进展

脓毒症是由宿主对感染反应失调引起的危及生命的器官功能障碍,作为人体重要器官,肺脏极易在脓毒症时发生损伤,导致急性呼吸窘迫综合征(ARDS)的发生。脓毒症引起的 ARDS发病机制非常复杂,其确切发病机制尚不完全清楚,涉及多个信号通路被激活。本文主要综述目前研究较多的信号通路在脓毒症相关急性肺损伤(ALI)/ARDS中的作用及机制,分析信号通路不同蛋白质和基因之间的相互作用,以及不同信号通路之间的关联性,以期为探寻脓毒症相关肺损伤治疗靶点提供一定理论基础。     

下尿路NO信号通路及其在脊髓损伤中的意义

一氧化氮（NO）是一种广泛的信号分子,在人体大多数器官系统的生理、病理过程中发挥着重要作用.目前对NO的研究较多.现就其在下尿路NO信号通路及其在脊髓损伤中的意义作一综述.     

骨碎补治疗骨质疏松症的实验研究进展

骨碎补作为补肾强骨、活血化瘀类的代表中药,被广泛应用于临床,尤其是在治疗骨质疏松症方面具有重要作用。关于骨碎补的基础研究已成为近年来的研究热点。众多学者从细胞生物学和分子生物学的方向出发,研究骨碎补对间充质干细胞、成骨细胞和破骨细胞分化水平的调节能力,并在信号传导通路方面探讨骨碎补通过BMP-Smads信号通路、OPG/RANKL/RANK信号通路、雌激素信号通路等对机体骨代谢水平的调控机制。大量的实验研究从不同层面论证了骨碎补在调节骨代谢平衡、改善骨质疏松方面的作用。虽然骨碎补在临床治疗与实验中被广泛研究,但是其对于细胞的机制研究及信号通路研究仍待总结,尤其是对于激活还是抑制Notch信号通路来发挥作用尚需进一步深入探究。     

Notch信号通路在骨髓间充质干细胞向成骨细胞分化过程中的作用

MSC(Mesenchymal stem cell)具有多向分化潜能和自我增殖能力.在不同调节因子的作用下分化为多种细胞,如成骨细胞、软骨细胞、脂肪细胞、成肌细胞、神经细胞和血管内皮细胞等[1-3].MSC向Osteoblast(OB)分化的过程受到多种通路的调控和影响,如Notch、Wnt、MAPK等信号通路.本文结合最新研究进展,重点综述了Notch信号通路在MSC向OB分化过程中的调节作用.     

Notch信号通路在脊髓损伤中的研究进展

脊髓损伤是一种严重的中枢神经系统疾病,会引起一系列复杂的病理生理学变化,激活包括Notch信号在内的多种信号通路.研究证实Notch信号通路的激活不利于脊髓损伤后神经修复和症状改善,其机制包括抑制神经元分化和轴突再生,促进反应性星形胶质细胞增生,促进M1型巨噬细胞极化和促炎因子的释放,抑制新生血管的生成.因此,以抑制N...     

Notch信号通路在肿瘤中的研究进展

【摘要】 Notch信号通路是一条影响细胞命运、保守而重要的信号转导通路,几乎涉及所有细胞的生长活动,在调节细胞分化、增殖和凋亡,及在一系列生理、病理过程中都起着关键性的作用,并在肿瘤的发生、发展中也发挥了至关重要的作用。近年对Notch信号通路的研究不断加深和完善,使其与肿瘤的密切关系得到了充分呈现,并有望针对相关靶点设计靶向药物,为肿瘤治疗提供新方向。     

A role for Notch signaling in corneal wound healing

To identify the role of the Notch signaling pathway in corneal wound healing, rat corneas receiving either epithelial or stromal wounds were placed in organ culture for up to 3 and 14 days, respectively. Localization of Notch receptors—Notch1, Notch2, and their ligands—Delta1, Jagged1 was determined by immunofluorescence. Wounds were treated with a γ‐secretase inhibitor to suppress Notch signaling or recombinant Jagged1 to enhance Notch signaling and morphological changes in the epithelium and stroma were recorded. The expressions of markers of cell proliferation (Ki67) and epithelial differentiation (cytokeratin 3) were assessed by immunohistology. Notch1 and Notch2 were localized to suprabasal epithelial cells in normal corneas. During corneal wound healing, both Notch receptors were detected in suprabasal and superficial epithelial layers. Delta1 and Jagged1 were observed throughout all corneal epithelial cell layers and occasional keratocytes of the stroma in normal and wounded corneas. γ‐secretase inhibition of Notch resulted in increased epithelial cell layers, with recombinant Jagged1 activation of Notch leading to a reduction in epithelial cell layers during corneal wound healing. Correspondingly, the activation of Notch resulted in a decreased cytokeratin 3 expression in the corneal epithelium, with no effect on cellular expression of Ki67. Notch signaling pathway suppressed corneal epithelial differentiation during corneal wound healing, but had no effect on epithelial cell proliferation.     

Repair problems in podocytes: wnt, notch, and glomerulosclerosis

Wnt/Ctnnb1 and Notch signaling play key roles in kidney development and epithelial cell specification. Recent reports have suggested that these pathways are reactivated in response to injury and in different disease conditions. Studies using genetically modified animal models showed that sustained activation of Notch and Wnt signaling in podocytes are causally related to albuminuria and glomerulosclerosis development. Here, we discuss the role and regulation of Wnt/Ctnnb1 and Notch signaling in podocytes.     

Notch信号转导通路与肿瘤分子靶向治疗研究进展

Notch信号转导通路与细胞增生、分化、凋亡密切相关,与肿瘤的关系日益受到关注,以Notch通路为靶点的肿瘤治疗策略显示了其广阔的应用前景.本文将从肿瘤中Notch通路的调控、分子靶向治疗机制及应用进展方面做一综述.     

Notch信号转导通路与肿瘤分子靶向治疗研究进展

Notch信号转导通路与细胞增生、分化、凋亡密切相关,与肿瘤的关系日益受到关注,以Notch通路为靶点的肿瘤治疗策略显示了其广阔的应用前景.本文将从肿瘤中Notch通路的调控、分子靶向治疗机制及应用进展方面做一综述.     

Hippo-Yap信号通路在肝脏疾病中的作用及其研究进展

河马（Hippo）信号通路最初作为一种抑制果蝇组织生长的通路被发现,主要由MST1/2、LATS1/2和Yap/TAZ三种激酶级联组成。随着研究的进展,在哺乳动物中Hippo信号通路的同源基因也得到了证实,并且在控制器官大小和其他生理功能当中也发挥着关键的作用。Hippo信号通路主要通过调控Yap的核移位发生相应的作用。当Hippo信号通路的上游激酶失活时,Yap/TAZ被去磷酸化并且能够作为转录共激活因子进入细胞核,与相应的转录因子结合发挥作用。既往Hippo-Yap信号通路研究主要集中于细胞命运、新陈代谢、肿瘤发生和免疫系统等方面。随着研究的逐步深入以及肝脏疾病的发生率逐步升高,Hippo信号通路在肝脏疾病的发生与发展过程中的相关研究取得一定的进展。笔者从多种临床常见相关肝脏疾病（胆汁淤积性肝损伤、肝缺血再灌注损伤、非酒精性脂肪性肝病、酒精性肝病、对乙酰氨基酚诱导肝损伤、肝纤维化以及肝癌）阐述Hippo-Yap信号通路在其中所发挥作用。     

内质网应激与细胞增殖关系研究进展

目的了解内质网应激在细胞增殖中的研究进展,为组织的损伤修复、器官的增殖再生等研究找到可靠的循证资料依据。方法复习近年来关于内质网应激相关的多条信号通路在细胞增殖和损伤修复中研究进展的相关文献并加以综述。结果内质网应激通过未折叠蛋白反应的3条途径在与白细胞介素-6、肿瘤坏死因子-α、血管内皮生长因子、Wnt等多种信号分子发生作用后,通过不同的途径参与了肠上皮细胞、骨骼肌细胞、肝细胞、胰岛细胞等多种不同组织细胞的增殖再生过程。结论尽管内质网应激在决定细胞命运这一领域的研究中众说纷纭,但通过近年来有关内质网应激对维持细胞存活和促进细胞增殖这一方面的研究进行回顾后分析发现了内质网应激在促进细胞增殖这一过程中的复杂性、多样性和重要性,它既能通过与Wnt蛋白这种经典的信号通路促进细胞增殖,也能独立于Notch通路之外通过与RNA结合蛋白Musashi蛋白作用发挥其修复组织、促进增殖的作用,这种复杂的反应通路在不同的细胞中与不同的促因子相互作用,为细胞增殖、损伤修复和器官再生的研究提供了研究的方向和探索的可能,让我们看到了内质网应激在细胞增殖中的巨大作用。     

Notch Signaling in Mammary Development and Oncogenesis

With the discovery of an activated Notch oncogene as a causative agent in mouse mammary tumor virus induced breast cancer in mice, the potential role for Notch signaling in normal and pathological mammary development was revealed. Subsequently, Notch receptors have been found to regulate normal development in many organ systems. In addition, inappropriate Notch signaling has been implicated in cancer of several tissues in humans and animal model systems. Here we review important features of the Notch system, and how it may regulate development and cancer in the mammary gland. A large body of literature from studies in Drosophila and C. elegans has not only revealed molecular details of how the Notch proteins signal to control biology, but shown that Notch receptor activation helps to define how other signaling pathways are interpreted. In many ways the Notch system is used to define the context in which other pathways function to control proliferation, differentiation, cell survival, branching morphogenesis, asymmetric cell division, and angiogenesis--all processes which are critical for normal development and function of the mammary gland.     

Pancreatic regeneration in chronic pancreatitis requires activation of the notch signaling pathway.

Chronic pancreatitis as an inflammatory process characterized by morphological changes, pancreatic dysfunction, and pain. During pancreatic injury and repair the Notch signaling pathway is reinstated. The current study analyzed this pathway in chronic pancreatitis and characterized its influence on fibrogenesis. Real-time quantitative PCR and immunohistochemistry were used for expression studies. Notch activation was determined by a specific luciferase-HES-1-reporter gene constructs. Cells were stimulated with alcohol, glucose, bile acids, and steroids. Notch-2, -3, and -4 mRNA, were overexpressed in chronic pancreatitis specimens. The ligands Jagged-1, -2, and Delta-1 were highly overexpressed. Jagged-1 and Notch receptors were observed in nerves, regenerating exocrine cells, and endocrine cells. Delta staining was present in ductal but not in acinus cells and not in nerves. Activation of Notch signaling was detectable upon cell stimulation with glucose, steroids, and bile acids. High glucose levels were further associated with increased collagen-I production. The Notch pathway is reactivated during chronic pancreatitis. Among the stimuli activating the Notch pathway are steroids, high glucose levels, and bile acids. These findings suggest a possible role of the Notch pathway during pancreatic regeneration since Jagged-1 inhibits inducible collagen-1 production, suggesting a new mechanism of tissue repair in this disease.