生长因子的调控机制研究

细胞生长调节因子,特别是其调控机制的研究是一十分活跃的领域。目前发现生物体内的生长调节因子,多数属于肽类物质。这些肽类生长因子及其受体与多种生理及病理状态,如生长,分化,免疫,肿瘤,创伤愈合等有关,因而受到广泛重视。1986年诺贝尔生理医学奖即授予肽类生长因子研究的开拓者Cohen,S和Levi-montacini。关于生长因子及其受体的生物化学,生长因子与肿瘤的关系,生长抑制因子的研究,以及生长因子研究的国内、外现状,已由另文“生长因子的研究进展”介绍。本文则对肽类生长因子的作用机理,亦即其生长调控机制作进一步阐明。     

TIEG与肿瘤的发生发展

β-转化生长因子(transforming growth factor-β,TGF-β)诱导的早期反应基因(TGF-β inducible early gene,TIEG)产物是Sp1样转录因子家族的新成员。TIEG亚家族共有3个成员:TIEG1、TIEG2和TIEG3。TIEG作为一个转录因子,能够调节多个与细胞生长分化有关的基因的表达。近年来研究发现,TIEG异常表达与多种肿瘤的发生发展有关,如乳腺癌、肺癌、胰腺癌、卵巢癌和胃癌;并且最新的研究发现,在某些抗癌药物作用过程中TIEG的表达也明显上调。这些研究结果表明,TIEG可能是一个重要的肿瘤抑制因子,因此有必要对其进行深入研究,有助于加深对肿瘤发生机制的了解。     

转化生长因子β的生物学特性、功能及其临床应用前景

转化生长因子β是一种高度多效性,多功能性的生长与分化因子,它广泛地调节机体的生长,发育,炎症,修复和免疫等许多生理和病理过程,具有重要的生物学功能和广阔的临床应用前景。     

SOCS家族在中枢神经系统的研究进展

细胞因子信号抑制因子（SOCS）家族是一类对细胞因子信号通路具有负反馈调节作用的蛋白分子,参与多种细胞因子、生长因子和激素的信号调节。细胞因子对中枢神经系统中的各种生物效应具有广泛多样的调节作用,SOCS家族的许多成员在发育时期和成年的脑内均有表达,SOCS家族不仅与细胞因子信号调节及中枢神经系统多种功能的调节密切相关,而且可能是神经发育和分化的重要调控因子,并参与神经免疫内分泌调节。本文综述了SOCS家族的发现、结构特点、脑内分布以及在中枢神经系统中的功能等方面的研究进展。     

MicroRNA-126(miR-126)对血管调节的分子机制

脉管系统的结构,维护及重塑的精确调节对于血管的正常发育,组织损伤的应答和肿瘤的生长都是必不可少的。最近,越来越多的研究报道了非编码的RNAs,又叫做microRNAs调节内皮细胞对血管原刺激的应答反应。在体内,维持血管内皮细胞和血管的完整性方面miR-126是一种重要的血管生成信号调节因子。miR-126通过负性调控血管生长因子促进血管发生反应,这些血管因子包括血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)。因此,miR-126表达的靶向作用也许对于血管过多或缺乏引起的相关疾病开辟了一种新的治疗方法,这些发现也证实了单一miRNA能够调节血管的完整性及血管生成,为调整血管的形态和功能提供了一个新的靶点。本文就当前miR-126对血管的调节及分子机制进行综述。     

转化生长因子—β超家族成员的信号传导通路

转化生长因子-β超家族是在无脊椎动物和脊椎动物中高度保守的一类细胞因子,其家族成员参与调节细胞的增殖、凋亡、分化和发育等多种生命活动。具有丝氨酸／苏氨酸激酶活性的Ⅰ型受体和Ⅱ型受体共同介导了转化生长因子-β超家族成员的跨膜信号传导。新近克隆鉴定的Smad蛋白家族负责将信号由细胞膜传导到细胞核。Smad介导的信号传导通路同其他信号传导通路之间存在相互调节。转化生长因子-β超家族的信号传导通路异常与肿瘤的发生有密切关系。     

表皮生长因子家族及其在海胆中的研究进展

表皮生长因子家族(Epidermal growth factor family)是一组具有与表皮生长因子(Epidermal Growth Factor,EGF)较高同源结构及相似生物学功能的糖蛋白,均为EGF受体的配体,具有调节胚胎细胞生长和分化以及与移动的细胞外基质蛋白相互作用等特点.综述了海胆EGF家族成员的基本生物学特性及其EGF相关蛋白家族的研究进展.     

IGF系统的生物学功能及其与肿瘤的关系

胰岛素样生长因子（insulin-like growth factor,IGF)是体内重要的生长因子。它对组织细胞的增殖。分化,凋亡,机体的生长发育及肿瘤的发生发展起重要的调节作用。IGF系统的组成包括;IGF-Ⅰ,IGF-Ⅱ,IGF-ⅠR,IGF-ⅡR,IGFBP家族,IGF促增殖,促生长的活性主要由IGF-IR介导;IGF-ⅡR的主要作用是清除游离IGF-Ⅱ,调节IGF-Ⅱ的水平,IGFBP1-6是IGFs活性的调节因子。近年的研究表明它们也有不依赖IGF的生物活性。     

卵泡生长发育的调节因子

胎儿期卵巢中的卵泡仅有一小部分能发育到成熟并排卵,大多数卵泡都要发生闭缩。闭缩发生在卵泡生长发育的各个阶段,在不同阶段,调节卵泡分化的因子是各不相同的,本文综述了在卵泡生长发育各个阶段的调节因子,主要包括内分泌因子,局部分泌因子和细胞内的调节因子。原始卵泡闭缩是卵泡褪化的主要原因;在低速生长的腔前卵泡阶段,局部会产生一些生长因子,这些因子能够促进卵泡生长发育,抑制其闭缩,腔室卵泡阶段,是卵泡生长发育最重要的阶段,在该阶段,FSH是其重要的调节因子。另外,胰岛素类生长因子1和白细胞介素1β也是腔室卵泡阶段的重要调节因子,排卵前卵泡能够表达促黄体激素受体,促黄体激素和其受体是此阶段卵泡存活的调节因子。但是,对黄体波和排卵间的时间了解甚少。在此阶段,孕激素是卵泡存活的调节因子。     

生长分化因子15及其特异性受体GFRAL信号通路

生长分化因子15（growth differentiation factor 15, GDF15）属于转化生长因子β（transforming growth factor-β, TGF-β）超家族的成员之一,是与转化生长因子β家族成员同源性很低的新一类二聚体多肽。GDF15最初发现于活化的巨噬细胞中,可通过2种不同的细胞途径分泌进入机体循环。GDF15作为一种应激蛋白质,广泛参与到例如磷酸肌醇3激酶/蛋白激酶B、细胞外信号调节激酶、c-Jun氨基末端激酶及核因子-κB等多种信号通路,调节着各种疾病进程。作为一种新型应激分子,GDF15在肥胖、体重减轻、癌症发展、心血管疾病、炎症和自身免疫疾病有着调控及生物标志的作用。胶质细胞源性神经营养因子（glial-derived neurotrophic factor, GDNF）样受体α（GDNF receptor alpha-like, GFRAL）为GDF15的特异性受体。GDF15活性发挥的分子基础是通过GFRAL依赖结合成多聚体来传导信号。GDF15-GFRAL信号通路的干预在减肥药物和癌症愈后恢复的药物开发中有着良好的应用潜力。本文阐述了GDF15 GFRAL信号通路的最新研究动态,概括了GDF15和GFRAL的分子结构,重点介绍GDF15 GFRAL信号通路的作用机制,揭示疾病发生发展中GDF15作为生物标记物的作用和调节能力,展望了调节GDF15-GFRAL信号通路在相关疾病的研究潜力和治疗策略。     

The growth of growth

Over a 40-year period, 1940 through the present, human growth research has increased from a minimal to a major part of physical anthropology. Such research, originally conducted at the major American growth centers, has become more diverse and more specialized, extending to National Probability Samplings, nutritional surveys, studies of twins, investigations restricted to the craniofacial complex, and studies of the growth and development of various primate species. Besides extending knowledge of growth and development in general and control mechanisms in particular, there has been major feedback into physical anthropology affording far greater understanding of human variability, of taxonomic differences, and of changes previously believed to be phylogenetic in nature. To the larger extent, all physical anthropologists have some degree of growth awareness.     

From growth arrest to growth suppression.

Since the introduction of the cell cycle concept two approaches to study growth regulation of cells have been proposed. One claims that cells are naturally quiescent, requiring a stimulatory encouter with growth factors for induction of cell division. The other considers cellular multiplication as the natural steady-state; cessation of multiplication is thus a restriction imposed on the system. In the latter case emphasis is mainly on the signals involved in arrest of multiplication. This Prospect focuses on specific events occurring in mammalian cells at growth arrest, senescence, and terminal differentiation, specifically emphasizing the growth inhibitory factors, tumor suppressor genes, and other signals for growth suppression.     

Measuring growth rate in high-throughput growth phenotyping

Growth rate is an important variable and parameter in biology with a central role in evolutionary, functional genomics, and systems biology studies. In this review the pros and cons of the different technologies presently available for high-throughput measurements of growth rate are discussed. Growth rate can be measured in liquid microcultivation of individual strains, in competition between strains, as growing colonies on agar, as division of individual cells, and estimated from molecular reporters. Irrespective of methodology, statistical issues such as spatial biases and batch effects are crucial to investigate and correct for to ensure low false discovery rates. The rather low correlations between studies indicate that cross-laboratory comparison and standardization are pressing issue to assure high-quality and comparable growth-rate data.     

Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth

To examine the relationship between growth hormone (GH) and insulin-like growth factor 1 (IGF1) in controlling postnatal growth, we performed a comparative analysis of dwarfing phenotypes manifested in mouse mutants lacking GH receptor, IGF1, or both. This genetic study has provided conclusive evidence demonstrating that GH and IGF1 promote postnatal growth by both independent and common functions, as the growth retardation of double Ghr/Igf1 nullizygotes is more severe than that observed with either class of single mutant. In fact, the body weight of these double-mutant mice is only approximately 17% of normal and, in absolute magnitude ( approximately 5 g), only twice that of the smallest known mammal. Thus, the growth control pathway in which the components of the GH/IGF1 signaling systems participate constitutes the major determinant of body size. To complement this conclusion mainly based on extensive growth curve analyses, we also present details concerning the involvement of the GH/IGF1 axis in linear growth derived by a developmental study of long bone ossification in the mutants.     

Cranial growth and growth dimorphism in Ateles geoffroyi

With the exception of the work of Schultz (1960), cranial growth in Ateles is not well documented. This paper describes the results of a detailed quantitative study of cranial ontogeny in male and female Ateles geoffroyi. Using Euclidean Distance Matrix Analysis (EDMA), local areas of form change due to growth within spider monkey crania are identified. We found substantial change local to the zygomatic region in the face, identified mediolaterally directed changes in the palate, detected relatively larger amounts of change local to the anterior neurocranium compared to the posterior neurocranium, and demonstrate a greater amount of basicranial growth along a mediolateral axis than previously reported. Cranial sexual dimorphism is also examined. A. geoffroyi is noted for being monomorphic, and we found a general similarity between male and female cranial forms at all developmental ages. However, differences in overall cranial size between the sexes were found in the oldest subadult age group but not between male and female adults. This difference suggests that A. geoffroyi females attain their adult cranial form slightly before males and implies a pattern of earlier onset of female maturity relative to males. © 1993 Wiley-Liss, Inc.     

Insulin-like growth factor inhibition of growth hormone secretion

Somatomedins-insulin-like growth factors (SM/IGF) are growth hormone (GH) dependent serum growth factors. There is some evidence that IGF inhibit GH release (negative feedback) in 3- to 24-h incubations of cultured rat adenohypophysial cells. We have used acutely dispersed noncultured rat adenohypophysial cells to study the dynamics of IGF on GH secretion. In this system both IGF-I and IGF-II (100 ng/mL) slightly, but significantly, decrease the cumulative GH released by human pancreas growth hormone releasing factor 1-40 (GRF) and the phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine. The inhibition is small (16%) and usually not statistically significant until 2 h of incubation. The inhibition with IGF is additive to that produced with low concentrations of somatostatin. The IGF also significantly decrease the rate of GH release in all time periods tested (0-1, 1-2, 2-3 h). In addition, the IGF decrease the quantity of [14C]leucine protein eluted at the position of labelled rat GH on Sephadex G75, which would include newly synthesized GH extracted from the cells. Thus we conclude that the decreased GH released may be due to an effect of IGF on both rate of release and on GH synthesis.     

Polypeptide growth factors in embryogenesis and tumor growth

Polypeptide growth factors, which belong to different families (epidermal growth factors, insulin-like growth factors, fibroblast growth factors, transforming growth factors-beta, and some others), were characterized regarding their specific role in embryogenesis and tumor growth. Differences and parallels of the functioning of growth factors in these processes have been noted. Potential significance of the described characteristics of growth factors for directed modulation of embryogenesis and tumor growth is discussed.