Nuclear localization of mouse fibroblast growth factor 2 requires N-terminal and C-terminal sequences

In vertebrates, different isoforms of fibroblast growth factor 2 (FGF2) exist, which differ by their N-terminal extension. They show different localization and expression levels and exert distinct biological effects. Nevertheless, genetic inactivation of all FGF2 isoforms in the mouse results in only mild phenotypes. Here, we analyzed mouse FGF2, and show that, as in the human, mouse FGF2 contains CTG-initiated high molecular-weight (HMW) isoforms, which contain a nuclear localization signal, and which mediate localization of this isoform to the nucleus. Using green fluorescent protein-FGF2 fusions, we furthermore observed, that C-terminal deletions disable nuclear localization of the short low-molecular-weight (LMW) 18-kDa isoform. This loss of specific localization is accompanied by a loss in heparin binding. We therefore suggest that, first, localization of mouse FGF2 is comparable to that in other vertebrates and, second, FGF2 contains at least two sequences important for nuclear localization, a nuclear localization sequence at the N terminus which is only contained in the HMW isoform, and another sequence at the C terminus, which is only required for localization of the LMW 18-kDa isoform. Received 1 July 2003; accepted 14 August 2003     

成纤维细胞生长因子23在慢性肾脏疾病血磷代谢中的作用

 成纤维细胞生长因子23(FGF23)是近年来发现的由骨细胞产生的一种激素,主要作用是抑制肾小管磷重吸收和1,25(OH)₂D循环水平。慢性肾脏疾病(CKD)是世界范围内影响数百万人的公共卫生疾病。FGF23循环水平升高导致的血磷稳态失调是CKD早期和普遍的并发症。本文综述FGF23家族结构、FGF23在调节磷和维生素D代谢中的作用及其合成和分泌的调控。重点介绍FGF23在CKD中与血钙、血磷及甲状旁腺激素(PTH)的作用机制,以及FGF23在评估CKD进展、预测预后中的作用。分析表明,FGF23可能成为慢性肾脏疾病骨和矿物质代谢中的重要诊断标志和治疗对象。     

骨质疏松患者FGF23与Crosslaps血清浓度检测与分析

目的:探讨骨质疏松症(Osteoporosis,OP)患者外周血成纤维生长因子23(Fibrobalst growth factor-23,FGF23)、Ⅰ互型胶原交联C末端肽(Crosslaps)与25-(OH)D代谢水平与骨质疏松症的关系.方法:选择骨质疏松女性患者32名,年龄48~90岁(OP组),与21名健康人年龄31~50岁(对照组).采用酶联免疫吸附法检测外周血FGF23,Crosslaps及25-(OH)D水平.采用全自动血液生化分析仪检测血钙、血清无机磷、碱性磷酸酶(Alkaline phosphates,ALP)水平,并对OP患者25-(OH)D与FGF23、Crosslaps、血钙、血磷的相关性进行分析.对53名受试者进行骨密度(Bone mineral density,BMD)测量及医学影像学检测.采集OP患者及健康人股骨骨样进行石蜡包埋、切片、HE染色并观察,采用病理学图像分析系统进行形态计量学分析.结果:与对照组比较,OP组患者血清中FGF23、Crosslaps水平显著升高(P0.05);OP患者血清中25-(OH)D水平与FGF23相关系数为-0.012 2,与Crosslaps相关系数为-0.231 7;通过骨组织形态计量学分析,OP患者骨小梁平均厚度、骨小梁面积百分率较对照组显著减少(P0.05),OP组骨小梁间距较对照组显著增大(P0.05).OP患者左侧股骨颈(Femeralneck,FN),Ward's三角(Ward's)骨密度值与对照组均有显著减少(P0.05).通过影像学检测发现OP组X光片透光度有所增加,骨小梁变细,骨皮质变薄.结论:骨质疏松症患者血清中FGF23,Crosslaps因子水平与25-(OH)D水平存在一定相关性.提示其在骨代谢所引起的血清水平变化,以及三者之间的关系可为骨质疏松症的诊断和治疗提供参考.     

环论中Faith三大猜测的进展

环论中的Faith三大猜测（FGF猜测、Faith-Menal猜测和Faith猜测）是指FGF－环、强右Johns环以及左完全右内射环均为QF环，其中R是右FGF－环指任一个有限生成右R－模或嵌入自由模的环，强右Jonhs环是指右Norther左FP－内射环，本文介绍了Faith三大猜测的历史背景及最新进展，给出了右CF－环及右Jonhs环为右Artin环的条件，提出了与三大猜测有关的一些公开问题。     

Perlecan: how does one molecule do so many things?

Perlecan is a large multi-domain extracellular matrix proteoglycan that plays a crucial role in tissue development and organogenesis. In vertebrates, perlecan functions in a diverse range of developmental and biological processes, from the establishment of cartilage to the regulation of wound healing. How can a single molecule modulate such a wide variety of processes? We suggest that perlecan employs the same basic mechanism, based on interactions with growth factors, morphogens and matrix proteins, to regulate each of these processes and that the local extracellular environment determines the function of perlecan and consequently its downstream effects on the structure and function of the organ. We discuss this hypothesis in relation to its role in three major vertebrate developmental processes: angiogenesis, chondrogenesis and endochondral ossification.     

关于 C2环的一个注记

左(右)G2环是指同构于直和项的左(右)理想也是直和项的环，这类环的研究是目前环论中的一个热点问题．其中之一是和FGF猜想紧密联系的．本文中给出了有关强右G2环和G2环的一个结论，为FGF猜测的研究提供一个新的方向．     

Molecular analysis of axonal target specificity and synapse formation

The development of neuronal connectivity requires the growth of axons to their target region and the formation of dendritic trees that extend into specific layers. Within the target region growth cones, the tips of extending axons are guided to finer target fields including specific subcellular compartments where they form synapses. In this article we highlight recent progress on molecular aspects of axonal subcellular target selection such as the axon initial segment or specific sublaminae of the vertebrate retina. We then discuss the very recent progress on the molecular analysis of synapse formation in the central nervous system, including the direction of differentiation into an inhibitory or excitatory synapse. Apparently, initial synaptic contacts are structurally and functionally modulated by neuronal activity, raising the question how neuronal activity can modify synaptic circuits. We therefore also focus on neural proteins that are up-regulated, secreted or converted by synaptic activity and, thus, might represent molecular candidates for experience-driven refinement or remodeling of synaptic connections. Received 5 July 2005; received after revision 19 August 2005; accepted 2 September 2005     

重组人成纤维细胞生长因子-8a在大肠杆菌中的可溶性表达

通过低温诱导,成功实现了重组人成纤维细胞生长因子-8a蛋白在大肠杆菌中的可溶性表达.进一步研究了温度、IPTC浓度、诱导时长、诱导时期(OD600)、培养基类型这5个因素对重组人成纤维细胞生长因子-8a蛋白可溶性表达的影响,确定了可溶性表达最优化条件.优化表达条件后实现可溶性表达率大干30%.     

High molecular weight FGF2: the biology of a nuclear growth factor

Fibroblast growth factor 2 (FGF2) is one of the most studied growth factors to date. Most attention has been dedicated to the smallest, 18kDa FGF2 variant that is released by cells and acts through activation of cell-surface FGF-receptor tyrosine kinases. There are, however, several higher molecular weight (HMW) variants of FGF2 that rarely leave their producing cells, are retained in the nucleus and act independently of FGF-receptors (FGFR). Despite significant evidence documenting the expression and intracellular trafficking of HMW FGF2, many important questions remain about the physiological roles and mechanisms of action of HMW FGF2. In this review, we summarize the current knowledge about the biology of HMW FGF2, its role in disease and areas for future investigation. Received 28 July 2008; received after revision 18 August 2008; accepted 22 August 2008