骨髓基质干细胞体外诱导分化为施旺细胞的研究进展

骨髓基质干细胞是一种具有多向分化潜能的细胞,除了分化为间充质细胞谱系外,还具有向非间充质细胞谱系如神经细胞分化的潜能,在体外适宜的条件下可以诱导分化为施旺细胞。多种抗氧化剂可以诱导骨髓基质干细胞分化为施旺细胞,分化所需时间较短;多种生长因子亦有同样的作用,诱导的施旺细胞传代时寿命延长;抗氧化剂和生长因子合用,分化施旺细胞的数量更多,传代时寿命更长。     

巨噬细胞极化信号通路及其调控机制研究进展

巨噬细胞是一类具有异质性和可塑性的免疫细胞,由单核细胞分化而来,在不同环境下可极化为不同的表型,分化中的巨噬细胞可位于极端分化的两型中的任意阶段。巨噬细胞在此极化过程中涉及较多的信号通路和转录调控,故本文将介绍具体巨噬细胞极化的通路及调控因子。     

Wnt信号通路与神经发生

W nt通路是细胞增殖分化的关键调控环节,在胚胎发育和肿瘤发生中起着重要作用。W nt途径参与了基因表达调节、细胞迁移粘附、细胞极化等过程,同时还与其它信号通路存在交叉协同。W nt/β-caten in通路在进化过程中高度保守,此通路的主要分子构成及相关调控机制已得到基本阐明。对神经系统而言,已有足够证据显示此通路参与了对神经前体细胞增殖,分化以及决定细胞命运的调控。近年更有研究显示,W nt/β-caten in途径对神经系统的发育包括皮层模式建立,突触形成等也是至关重要的。     

ERK信号通路的信号转导调控机制

胞外信号调控激酶（ERK）是发现的第1个丝裂原活化蛋白激酶（MAPK）,它调控多种重要的细胞生物学过程,包括细胞增殖、分化和凋亡等。ERK信号级联反应能够特异地介导广泛的生物学过程,其机制主要是通过信号的反馈调控,与支架蛋白的相互作用,亚细胞定位的改变,在级联反应的每一个环节存在不同功能的多种组分,细胞内非磷酸酶抑制物和G蛋白等的调控实现的。     

Notch信号通路研究进展

1917年,Morgan及其同事在果蝇体内发现一种基因,因其功能部分缺失可导致果蝇翅缘出现缺口,故命名该基因为Notch。随后的研究发现,Notch从无脊椎动物到脊椎动物的多个物种中表达,其家族成员的结构具有高度保守性,在细胞分化、发育中起着关键作用。迄今研究己阐明Notch信号通路的主要成员及核心转导过程,然而随着研究的深入,人们逐渐认识到该通路实际上处于十分复杂的调控网络之中,而这与其在发育过程中功能的多样性相符合。本文结合最新进展,系统阐述Notch信号通路的组成,功能,作用机制及调控,并揭示该通路异常与疾病的联系。     

mTOR信号通路与细胞凋亡

哺乳类动物雷帕霉素靶蛋白(mTOR)主要通过上游信号转导通路磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(PKB/Akt)/mTOR信号通路及下游信号通路mTOR/ eIF4E结合蛋白1(4EBP1)、mTOR/p70S6激酶(p70S6K)在细胞生长、增值与分化和在血管再生、蛋白合成与降解中发挥作用.细胞凋亡是细胞的一种程序性死亡,在机体发育、组织代谢中有着重要作用,而细胞凋亡的异常调节与许多疾病的发生和发展紧密相连.近年研究发现,mTOR信号通路在细胞凋亡过程中扮演了重要角色,并已被作为新的药物治疗靶点.     

调控巨噬细胞极化的相关信号通路及其调节机制研究进展

巨噬细胞是一群具有高度可塑性和异质性的免疫细胞,在维持免疫系统的稳定状态中扮演重要角色.不同刺激因子作用下,巨噬细胞可极化为M1型和M2型,其极化过程受多种信号通路共同影响.本文综述巨噬细胞极化过程涉及的主要信号通路及其调节机制的新进展.     

细胞外调节蛋白激酶信号通路在体外诱导神经干细胞向施万细胞分化中的作用

目的:探讨细胞外调节蛋白激酶(ERK)信号转导通路在体外诱导大鼠海马神经干细胞向施万细胞分化中的作用.方法:体外培养大鼠海马神经干细胞,向培养液中添加混和诱导剂诱导神经干细胞向施万细胞分化.将培养细胞分为2组,对照组采用含诱导剂的培养液进行培养,免疫印迹法检测ERK磷酸化水平,实验组中在此基础上添加ERK通路抑制剂U0126,免疫荧光双标染色计数胶质细胞特异性标记物S100及P75阳性细胞比例.结果:加入诱导剂后,磷酸化ERK1/2水平上升;3周后,可见P75、S100阳性的施万细胞.加入通路抑制剂后,实验组的ERK磷酸化水平逐渐降低.与对照组相比,实验组的施万细胞所占百分比明显减少.结论:ERK通路在神经干细胞向施万细胞的诱导分化中起重要作用.     

Wnt信号通路与胸腺发育

胸腺是人体重要的中枢淋巴器官,是T淋巴细胞分化发育的场所。起源于骨髓的淋巴细胞祖细胞,在胸腺中历经阳性选择和阴性选择后发育为成熟的T细胞,然后通过血液循环参与外周细胞免疫。研究表明,Wnt信号通路广泛存在于胸腺上皮细胞和T细胞,它不但影响胸腺上皮细胞的形态、功能,而且对于维持T细胞前体细胞和后期T细胞的分化发育都很重要。最近研究发现,Wnt信号通路参与了胸腺增龄性萎缩过程的调节,Wnt信号通路的改变可引起上皮网络结构的改变,最终导致胸腺微环境的破坏。因此,研究Wnt信号通路在胸腺发育中的作用,对于探索胸腺增龄性萎缩的调控机制和改善老年人的健康状况有重要意义。     

Integration of Cardiac Myofilament Activity and Regulation with Pathways Signaling Hypertrophy and Failure

The syndrome of congestive heart failure (CHF) is an entity of ever increasing clinical significance. CHF is characterized by a steady decrease in cardiac pump function, which is eventually lethal. The mechanisms that underlie the decline in cardiac function are incompletely understood. A central theme in solving the mystery of heart failure is the identification of mechanisms by which the myofilament contractile machine of the myocardium is altered in CHF and how these alterations act in concert with pathways that signal cell growth and death. The cardiac myofilaments are a point of confluence of signals that promote the hypertrophic/failure process. Our hypothesis is that a prevailing hemodynamic stress leads to an increased strain on the myocardium. The increased strain in turn leads to miscues of the normal physiological pathway by which heart cells are signaled to match and adapt the intensity and dynamics of their mechanical activity to prevailing hemodynamic demands. These miscues result in a maladaptation to the stressor and failure of the heart to respond to hemodynamic loads at optimal end diastolic volumes. The result is a vicious cycle exacerbating the failure. Cardiac myofilament activity, the ultimate determinant of cellular dynamics and force, is a central player in the integration and regulation of pathways that signal hypertrophy and failure. © 2000 Biomedical Engineering Society. PAC00: 8719Hh, 8719Ff, 8719Xx, 8719Rr, 8717-d     

细胞老化相关信号途径

细胞老化是正常细胞在受到各种类型的压力刺激后引发的一种程序性反应,表现为永久性细胞周期停滞。细胞老化可能促进生物衰老,并且与肿瘤发生受抑密切相关。至今已知的细胞老化相关信号途径主要有两条,分别是:p53-p21-pRb途径和p16-pRb途径。肿瘤抑制物p53和pRb分别是这两条途径的核心,二者突变在介导细胞老化逃逸、肿瘤发生中起着关键作用。     

Signaling Pathways in Cancer and Embryonic Stem Cells

Cancer cells have the ability to divide indefinitely and spread to different parts of the body during metastasis. Embryonic stem cells can self-renew and, through differentiation to somatic cells, provide the building blocks of the human body. Embryonic stem cells offer tremendous opportunities for regenerative medicine and serve as an excellent model system to study early human development. Many of the molecular mechanism underlying tumorigenesis in cancer and self-renewal in stem cells have been elucidated in the past decade. Here we present a systematic analysis of seven major signaling pathways implicated in both cancer and stem cells. We present on overview of the JAK/STAT, Notch, MAPK/ERK, PI3K/AKT, NF-kB, Wnt and TGF-β pathways and analyze their activation status in the context of cancer and stem cells. We focus on their role in stem cell self-renewal and development and identify key molecules, whose aberrant expression has been associated with malignant phenotypes. We conclude by presenting a map of the signaling networks involved in cancer and embryonic stem cells.     

High-Throughput Analysis of Tumor Necrosis Factor Signaling Pathways in Eight Cell Types during Rat Hepatic Regeneration

This study aims to clarify the relevance of tumor necrosis factor (TNFs) signaling pathways and liver regeneration (LR) at the cellular level. Eight liver cell types were isolated using Percoll density gradient centrifugation and immunomagnetic beads methods. Expressions of TNF signaling pathway-involved genes in each cell type after 2/3 hepatectomy (PH) were detected using gene chip. Results show the following: gene TNFα was upregulated in most cell types, especially in Kupffer cells (KC); TNFβ expression was insignificantly changed in eight liver cell types; the majority of genes involved in four TNFα signaling pathways showed increased expression during LR in hepatocytes (HC); TNFα-induced NFκB pathway-involved genes were upregulated preferentially between 2 and 24 h during LR in biliary epithelial cells (BECs); and TNFα-induced apoptotic pathway genes were downregulated preferentially at progressing phase of LR in dendritic cells (DCs). Referring to the above results, TNFα-mediated signaling pathways, in contrast to TNFβ, play the more proactive role in LR, and four TNFα-mediated signaling pathways seem helpful to regulate biological events in HC; BEC proliferation was partly controlled by TNFα-mediated NFκB pathway; and the impaired TNFα-mediated apoptotic pathway in DCs might contribute to the restoration of DC mass after PH. Briefly, the comparative analysis of genomewide expression profiles of TNF signaling pathways between different cell types is helpful in understanding the implication of TNF signaling in LR at the cellular level.     

Schwann细胞与其培养纯化

Schwann细胞是周围神经系统的主要功能细胞 ,兼有迁移、粘着、产生细胞外基质、形成髓鞘 ,参与周围神经修复的功能和分泌多种神经因子、生物活性物质 ,促进神经元、神经胶质细胞存活、抑制其凋亡的功能。短时间大量培养纯化Schwann细胞可为周围神经系统疾病的医疗寻求有效途径