Follistatin-like protein 1的生物学作用及其研究进展

Follistatin-like protein 1(FSTL1)是一种细胞外的糖蛋白,其参与细胞多种生物学过程,包括细胞增殖、凋亡、新陈代谢、分化、免疫反应及内分泌功能等。FSTL1存在于在大部分哺乳动物中,可由多种细胞分泌。通过激活PI3K-Akt、雌激素受体及其信号通路等发挥作用。目前关于FSTL1在炎症反应中的作用尚不够明朗。近年FSTL1被认为参与了机体自身免疫性疾病、移植排斥及肿瘤等疾病的发生。因而,拓展FSTL1在临床上的研究有着重要意义。     

经典Wnt信号通路与神经退行性疾病关系的研究进展

Wnt信号通路调节多种基因的转录,参与调控生物体的生长、发育以及细胞的增殖、分化和凋亡等重要的生理病理过程。在神经退行性疾病中,经典Wnt信号通路发生改变影响神经元的增殖、分化或对神经元产生毒性作用,导致神经元功能损伤。因此,研究经典Wnt信号通路与神经退行性疾病的发病机制及其治疗的关系有重要意义。     

雌激素与脑功能

雌激素神经效应的分子机制主要是通过ERβ和ERα以二聚体形式与其伴侣分子结合,作用于靶基因启动子ERE,调节基因转录水平.雌激素对大脑神经元的多靶向调节作用包括具有突触效应,增加大鼠海马神经元棘突密度和神经传导作用;促进脑原性神经生长因子(BDNF)表达,使细胞再生和死亡达到平衡状态;具有对性发育过程中大脑神经内分泌组织分化的可塑作用,促进性分化和成熟;对神经元具有保护作用,改善认知功能和抑制神经元凋亡.     

小鼠脊髓发育与神经细胞凋亡

目的通过观察小鼠脊髓发育过程中神经元的增殖、分化与凋亡,探讨小鼠脊髓的发育过程及其调控机制。方法取妊娠第18天(E18)至生后第90天(P90)小鼠173只,用5’-溴脱氧尿嘧啶核苷(BrdU)技术标记增殖的神经干细胞,免疫荧光法(DCX,NeuN和Caspase8)标记脊髓中的新生神经元,成熟神经元和凋亡细胞。结果在胚胎与出生早期,BrdU阳性细胞均匀分布于小鼠脊髓各部位。随着小鼠日龄的增加,脊髓神经干细胞可以分化为神经胶质细胞与神经元。其后,位于神经管侧脑室的新生神经元向中间层(未来的灰质)迁移,逐渐分化为成熟神经元。最后,神经元向脊髓中央聚集,灰质呈现典型的"H"型。随着神经元的分化,一些凋亡神经细胞出现在新生神经元与成熟神经元中。荧光双标显示,大部分的凋亡神经细胞都是新生神经元,说明神经元凋亡常常发生在新生神经元中。统计学分析表明,DCX、NeuN、Caspase-8标记的阳性细胞数均随小鼠日龄的增加而减少,说明神经元的分化和凋亡在脊髓的发育过程中逐渐减少。结论在脊髓的发育过程中存在着神经元的增殖、分化与凋亡。三者相互协同,共同调节脊髓的形成与发育。     

E3泛素连接酶在神经系统发育过程中的调控作用

泛素化在细胞代谢、蛋白质定位和降解中发挥着重要作用，并参与细胞周期调控、增殖、凋亡以及DNA损伤修复等生命活动的调控。泛素蛋白酶体系统(Ubiquitin proteasome system, UPS)中包括一类E3泛素连接酶(E3 ubiquitin ligase),它与泛素和底物蛋白的结合密切相关。神经系统发育是一个连续且复杂的过程，包括神经细胞发生、分化和迁移等过程，E3泛素连接酶通过水解病理性蛋白，激活神经干细胞并调节其增殖分化水平及调控神经元形态等途径来调控神经发育过程。     

Notch信号与树突状细胞发育分化及功能调控

树突状细胞(DC)在免疫反应中发挥重要作用,Notch信号通路在胚胎期和出生后的发育过程中调节细胞增殖、分化和凋亡.Notch信号参与了DC发育分化及其功能调控,本文综述了Notch信号与DC发育分化、功能调控的研究进展.     

雌激素营养和保护神经元的作用机制

雌激素与神经营养因子一样,在促进神经元的分化和存活,保护神经元,维持正常的功能等方面有重要作用.雌激素替代治疗能保护胆碱能神经元,改善认知功能和记忆,但对其作用的机理尚未完全了解.一般认为通过神经营养因子及其受体的相互调节,作用于相应的信号转导途径.     

神经干细胞及其应用

神经干细胞是具有自我更新和多向分化潜能等特性的多能干细胞,可在自身基因和/或外来信号调节下最终分化为神经元和神经胶质细胞.神经干细胞系的建立为其应用提供了稳定和丰富的细胞源.神经干细胞具有广泛的应用前景,如通过颅内神经干细胞移植从解剖和功能修复神经系统疾病;以神经干细胞为载体表达目的基因进行神经科学基础研究和神经系统疾病的基因治疗等.     

胶质细胞源性神经营养因子对猴骨髓间充质干细胞分化为神经元样细胞的影响

背景：鉴于骨髓间充质干细胞体外分化为神经样细胞的最终研究目的,是将诱导后的细胞移植入体内参与损伤神经系统的修复过程,因此,保证移植细胞的活性显得十分重要。 目的：探讨胶质细胞源性神经营养因子对隐丹参酮体外诱导猴骨髓间充质干细胞分化为神经元样细胞的保护作用。 方法：以隐丹参酮为诱导剂诱导第8代猴骨髓间充质干细胞分化为神经元样细胞,应用流式细胞仪检测不同时段诱导细胞的凋亡百分比(每间隔0.5 h为1组,共12组)。选择细胞凋亡百分比较高的一个时段,观察添加不同质量浓度胶质细胞源性神经营养因子(0-100 μg/L,共11组)对诱导细胞凋亡的影响。 结果与结论：诱导后细胞凋亡百分比逐渐升高,约4 h时达到峰值,维持约1 h后下降(P < 0.05)。 随着胶质细胞源性神经营养因子质量浓度由0 μg/L提高到30 μg/L,细胞凋亡百分比逐渐下降(P < 0.05),当胶质细胞源性神经营养因子质量浓度超过30 μg/L后,细胞凋亡水平受胶质细胞源性神经营养因子质量浓度影响不再显著。结果可见胶质细胞源性神经营养因子在隐丹参酮体外诱导猴骨髓间充质干细胞分化为神经元样细胞过程中具有保护作用。     

bHLH转录因子与大脑皮质祖细胞分化

在大脑新皮质发育过程中 ,bHLH转录调控因子 (basichelix loop helixtranscripitionfactor)参与调节大脑皮质多能祖细胞的分化。前神经bHLH因子 (Mash1,Neurogenin1,andNeurogenin2 )活性增强和Hes、Id因子的活性相应的减弱引起皮质多能祖细胞由增殖状态向神经生成转变。神经元形成后 ,Hes因子的激活促进星形胶质细胞的分化 ,而前神经bHLH因子Ngn抑制星形胶质细胞的分化。bHLH因子Olig1和Olig2活性的增加和Id活性的减弱启动了少突胶质细胞的形成。     

高脂饮食诱导肥胖小鼠表达卵泡抑素样蛋白1与脂肪组织炎症和棕色脂肪的功能

目的 探讨卵泡抑素样蛋白1（FSTL1）在高脂饮食诱导的肥胖小鼠脂肪炎症中的作用,以及对棕色脂肪功能的影响。 方法 6周龄C57BL/6 J小鼠分为两组,每组8只,给予12周正常饮食（RD）和高脂饮食（HFD）饲养,每周称量小鼠体重,记录小鼠摄食量;12周后,进行糖耐量和胰岛素耐量的检测并取材,称量小鼠的皮下白色脂肪、肾周白色脂肪、附睾白色脂肪和棕色脂肪的重量;HE染色观察小鼠白色脂肪中的冠状结构（CLS）及小鼠棕色脂肪组织变化,RT-PCR分析小鼠附睾白色脂肪炎症因子、肿瘤坏死因子α（TNF-α)、白细胞介素6（IL-6）和白细胞介素10（IL-10）的表达,以及FSTL1的表达;Western blotting检测棕色脂肪解耦联蛋白1（UCP1）与FSTL1蛋白的表达。 结果 与RD小鼠相比,HFD组小鼠的体重增加,摄食量减少,不同部位脂肪重量显著增加,葡萄糖耐受能力显著降低,胰岛素敏感性显著下降,附睾白色脂肪观察到炎症反应CLS且附睾白色脂肪中炎症因子TNF-α、IL-6及IL-10表达显著增高, FSTL1表达亦显著增加。Western blotting结果显示,HFD小鼠的棕色脂肪组织中UCP1与FSTL1表达水平均显著性高于RD组。 结论 在高脂饮食诱导的肥胖小鼠中,FSTL1的表达可能与脂肪炎症因子的分泌增加及棕色脂肪的功能有一定相关性。     

Follistatin-like protein 1 and its role in inflammation and inflammatory diseases

Immunologic Research - Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein produced mainly by cells of mesenchymal origin. FSTL1 has been shown to play an important role during...     

Behavioral and genetic effects promoted by sleep deprivation in rats submitted to pilocarpine-induced status epilepticus

Neuroglobin (Ngb) is a hypoxia-inducible protein with cytoprotective effects in animal models of stroke, Alzheimer's disease, and related disorders, but the molecular mechanisms involved in its induction are unknown. We tested the hypothesis that hypoxia-inducible factor-1 (HIF-1) regulates Ngb levels, using shRNA-mediated knockdown and lentiviral vector-mediated overexpression of the HIF-1α subunit, in cultured neural (HN33) cells. HIF-1α knockdown decreased and HIF-1α overexpression increased Ngb levels, consistent with a connection between HIF-1 and Ngb induction. These findings may have implications for understanding the hypoxia-response repertoire of neural cells and devising therapeutic strategies for neurologic disorders.     

Down-regulated FSTL5 promotes cell proliferation and survival by affecting Wnt/β-catenin signaling in hepatocellular carcinoma

Follistatin-like 5 (FSTL5), a member of the follistatin family of genes, encodes a secretory glycoprotein. Previous study revealed that it might play a suppressive role in hepatocellular carcinoma (HCC). However, its clinical significances, biological functions and molecular mechanisms in HCC development are poorly understood. To gain insight to the functions of FSTL5 in HCC, We examined FSTL5 expression pattern in 117 HCC tissue samples. The results of immunohistochemical staining analysis showed that FSTL5 is more commonly down-regulated in HCC compared to adjacent tissues and further clinicopathological analysis showed that its expression level is closely correlated with tumor size, TNM stage, local infiltration and patient prognosis. Both gain function assays and recombinant human FSTL5 protein treatment assays in vitro revealed that over-expressing FSTL5 could inhibit the abilities of cancer cell proliferation and survival. Further, we found that those effects on HCC growth and survival are associated with Wnt/β-catenin signaling. Taken together, all of our results validate that FSTL5 plays a suppressive role in HCC and suggest that down-regulated FSTL5 could elevate abilities of growth and survival of HCC cells by activation of Wnt/β-catenin signaling.     

Oscillatory control of Delta-like1 in cell interactions regulates dynamic gene expression and tissue morphogenesis

Notch signaling regulates tissue morphogenesis through cell–cell interactions. The Notch effectors Hes1 and Hes7 are expressed in an oscillatory manner and regulate developmental processes such as neurogenesis and somitogenesis, respectively. Expression of the mRNA for the mouse Notch ligand Delta-like1 (Dll1) is also oscillatory. However, the dynamics of Dll1 protein expression are controversial, and their functional significance is unknown. Here, we developed a live-imaging system and found that Dll1 protein expression oscillated in neural progenitors and presomitic mesoderm cells. Notably, when Dll1 expression was accelerated or delayed by shortening or elongating the Dll1 gene, Dll1 oscillations became severely dampened or quenched at intermediate levels, as modeled mathematically. Under this condition, Hes1 and Hes7 oscillations were also dampened. In the presomitic mesoderm, steady Dll1 expression led to severe fusion of somites and their derivatives, such as vertebrae and ribs. In the developing brain, steady Dll1 expression inhibited proliferation of neural progenitors and accelerated neurogenesis, whereas optogenetic induction of Dll1 oscillation efficiently maintained neural progenitors. These results indicate that the appropriate timing of Dll1 expression is critical for the oscillatory networks and suggest the functional significance of oscillatory cell–cell interactions in tissue morphogenesis.     

Zebrafish wnt3 is expressed in developing neural tissue

Wnt signaling regulates embryonic patterning and controls stem cell homeostasis, while aberrant Wnt activity is associated with disease. One Wnt family member, Wnt3, is required in mouse for specification of mesoderm, and later regulates neural patterning, apical ectodermal ridge formation, and hair growth. We have identified and performed preliminary characterization of the zebrafish wnt3 gene. wnt3 is expressed in the developing tailbud and neural tissue including the zona limitans intrathalamica (ZLI), optic tectum, midbrain‐hindbrain boundary, and dorsal hindbrain and spinal cord. Expression in these regions suggests that Wnt3 participates in processes such as forebrain compartmentalization and regulation of tectal wiring topography by retinal ganglia axons. Surprisingly, wnt3 expression is not detectable during mesoderm specification, making it unlikely that Wnt3 regulates this process in zebrafish. This lack of early expression should make it possible to study later Wnt3‐regulated patterning events, such as neural patterning, by knockdown studies in zebrafish. Developmental Dynamics 238:1768–1795, 2009. © 2009 Wiley‐Liss, Inc.     

Lack of lipid phosphate phosphatase-3 in embryonic stem cells compromises neuronal differentiation and neurite outgrowth

Background: Bioactive lipids such as lysophosphatidic acid (LPA) and sphingosine‐1‐phosphate (S1P) have been recently described as important regulators of pluripotency and differentiation of embryonic stem (ES) cells and neural progenitors. Due to the early lethality of LPP3, an enzyme that regulates the levels and biological activities of the aforementioned lipids, it has been difficult to assess its participation in early neural differentiation and neuritogenesis. Results: We find that Ppap2b^?/? (Lpp3^?/?) ES cells differentiated in vitro into spinal neurons show a considerable reduction in the amount of neural precursors and young neurons formed. In addition, differentiated Lpp3^?/? neurons exhibit impaired neurite outgrowth. Surprisingly, when Lpp3^?/? ES cells were differentiated, an unexpected appearance of smooth muscle actin‐positive cells was observed, an event that was partially dependent upon phosphorylated sphingosines. Conclusions: Our data show that LPP3 plays a fundamental role during spinal neuron differentiation from ES and that it also participates in regulating neurite and axon outgrowth. Developmental Dynamics 241:953–964, 2012. © 2012 Wiley Periodicals, Inc.