Notch信号通路在皮肤病的研究进展

Notch信号通路是一条进化上十分保守的信号转导系统.Notch受体与相邻细胞的配体相互作用转导细胞信号,从而影响细胞的增殖、分化和凋亡.较多文献表明,Notch信号通路在维持皮肤正常生理功能以及炎症性皮肤病、自身免疫性皮肤病、皮肤肿瘤、色素性皮肤病等多种皮肤病中发挥重要作用.尽管目前临床应用尚不成熟,Notch信号抑制剂和激活剂有希望为皮肤病的治疗提供新思路.     

点状自体皮肤移植及自体表皮移植治疗斑驳病

迄今对于白癜风和斑驳病等色素障碍性皮肤病尚无有效的治疗方法,使用适当的方法将带有黑素细胞的皮肤或表皮移植到白斑处,使色素再现是切实可行的。我们从1993年起开始此项工作,并首先在一例斑驳病患者身上获得成功,现报告如下。     

P物质-神经激肽1受体通路与白癜风

白癜风是一种常见的皮肤病,心理因素在白癜风的病因、发病过程以及疾病的演变和治疗中所起的重要作用已经越来越受到人们的重视。该文对国内外文献进行综述,归纳了心理因素与白癜风之间的关系,揭示了神经肽在皮肤黑素合成中的作用,提出P物质-神经激肽(SP-NK)1受体通路及其下游信号途径可能参与黑素细胞中黑素的合成,进而影响皮肤黑素的沉着。这些新发现支持了白癜风的神经与心理因素发病理论,同时提示神经肽及其受体可能成为色素障碍性皮肤病治疗的新靶点,具有重要的研究意义。     

中药的抗氧化作用治疗白癜风研究进展

白癜风是一种以皮肤出现大小形态不等的白色斑片、边缘清楚为特征的后天获得的色素脱失性皮肤病,黑素细胞的功能障碍或缺失,使皮肤和黏膜色素产生减少或消失.近年来对白癜风发病机制的多项研究证明,氧化应激可能是白癜风发生发展的一个重要因素.     

皮肤肿瘤

20100638Notch信号通路与皮肤肿瘤的研究现状(综述)/刘之力(大连市皮肤病医院皮肤科),李宏∥国际皮肤性病学杂志.-2009,35(5).-330～332Notch受体是脊椎动物和无脊椎动物发育过程中一类十分重要的信号受体蛋白家族,它通过与邻近细胞间的相互作用来精确调控各谱系细胞的分化,近年来发现其在个体系统发育、模式形成、肿瘤发生以及神经退行疾病等生理病理过程中起着重要的作用。目前,在Notch信号转导与调控及其与某些相关疾病,特别是与皮肤肿瘤的关系等方面的研究取得一定的进展。综述Notch的组成、结构及生物学功能;Notch信号转导和激活途径;Notch信号转导通路与肿瘤;Not     

Notch信号通路与皮肤肿瘤的研究现状

目前认为皮肤肿瘤的发生是一个多因素作用、多基因参与、经过多个阶段才最终形成的极其复杂的生物学现象.近年发现,皮肤肿瘤中存在Notch信号转导通路的异常,研究Notch信号通路的异常与皮肤肿瘤的相瓦关系,对皮肤肿瘤发病机制的阐明具有一定意义.     

遗传性泛发性色素异常症7例及家系调查

报告1例遗传性泛发性皮肤色素异常症及家系调查.患者男,18岁.因全身皮肤色素沉着伴色素减退18年就诊.头面部、躯干、四肢和手足背面弥漫性密集分布褐色色素沉着斑,其间夹杂大量色素脱失斑,牙龈和足跖部少量褐色色素沉着斑.色素沉着处组织病理检查示基底层色素增加,黑素细胞数目正常;色素减退处组织病理检查示基底层色素减少,黑素细胞数目亦正常.     

干细胞在皮肤科的应用

由于干细胞具有多种分化潜能及高度增殖能力的生物学特性,使其日益成为生物医学领域的研究热点.目前在色素障碍性皮肤病、遗传性皮肤病、红斑狼疮、蕈样肉芽肿、皮肤缺损、系统性硬化症、银屑病等皮肤科相关疾病中开展了多项干细胞的基础及临床应用研究.     

几种遗传性色素性疾病临床与分子遗传学研究进展

几种以常染色体显性遗传方式为主的遗传性色素性疾病在临床表现和分子遗传学方面研究取得重要进展,包括屈侧网状色素异常、遗传性泛发性色素异常症、家族性进行性色素沉着症以及家族性进行性色素沉着和色素减退症。屈侧网状色素异常由KRT5基因（12q13．13）功能丧失性突变所致;SASH1（6q24．2-q25．2）、ABCB6基因（2q33．3-q36．1）突变与常染色体显性遗传性泛发性色素异常症发病有关,而常隐类型致病基因定位于12q21-q23;家族性进行性色素沉着症由KITLG基因（12q21．12-q22）或19p13．1-pter区域内基因突变所致。家族性进行性色素沉着和色素减退症的发病与KITLG基因突变有关。以上基因突变主要通过影响黑素降解、黑素细胞迁移、黑素合成或黑素母细胞增殖等引起皮肤色素沉着异常。     

遗传性泛发性色素异常症1例

报告1例遗传性泛发性色素异常症的17岁男性患者，母亲左下腹有局部色素异常的表现。患者全身泛发色素沉着斑间以色素减退班，局部呈网状外观。HE染色示色素沉着区基底层细胞中黑色素增加，色素减退区黑素减少或缺如，而黑素细胞并不减少。人黑素细胞抗原HMB-45免疫组化示色素沉着区黑素细胞胞浆内有致密的阳性颗粒，而色素减退区黑素细胞胞浆内阳性颗粒少见。     

Melanoblasts' proper location and timed differentiation depend on Notch/RBP-J signaling in postnatal hair follicles

The Notch/RBP-J pathway is involved in a variety of developmental processes and in tissue homeostasis. In the melanocyte lineage, it has been shown that Notch signaling acts through Hes1 to maintain the melanocyte stem cell population in the hair follicle. This study was designed to determine whether Notch signaling is implicated in other steps of melanocyte-lineage postnatal development. For this purpose, we developed mice in which the RBP-J gene was conditionally ablated in the melanocyte lineage and used the Dct-lacZ reporter transgene to track melanocytes and their precursors in individual hair follicles. We determine that Notch/RBP-J-deficient melanoblasts are in reduced number within the hair follicle and gather within its lower permanent part. Moreover, our results show that Notch signaling is necessary to prevent differentiation of melanocyte stem cells and of melanoblasts before they reach the hair bulb. Finally, our data show that Notch signaling is involved in proper location of melanoblasts in the outer root sheath and of melanocytes in the hair matrix. These findings reveal previously unrecognized roles for Notch signaling in the melanocyte lineage.     

毛囊干细胞向黑素细胞系定向分化调控机制的研究进展

毛囊干细胞包含神经嵴来源的成体干细胞,具有多向分化潜能.利用毛囊干细胞模型,可以深入研究从神经嵴干细胞到成熟黑素细胞的定向分化过程和掌握黑素细胞前体阶段发育分化的调控机制,从而为理解色素性疾病的发生发展和恢复提供新的理论依据.概述近年来调控毛囊干细胞向黑素细胞系定向分化的相关细胞因子和信号通路的进展,以期为色素性皮肤病的发病和治疗发展提供新的方向和突破口.

Abstract：

Hair follicle stem cells contains pluripotent adult stem cells derived from the neural crest.With the experimental model of hair follicle stem cells,further studies could be carried out on the directed differentiation process of neural crest-derived stem cells into mature melanocytes,and on the regulatory mechanisms of melanocyte precursor differentiation,which will provide theoretical evidence for the understanding of development and recovery of pigmentary skin diseases.This article focuses on the recent advances in cytokines and signaling pathways regulating the differentiation from hair follicle stem cells into melanocyte lineage,which may provide directions for studies on the pathogenesis and treatment of pigmentary skin disorders.     

Notch and melanocytes: diverse outcomes from a single signal

Notch signaling is an evolutionally conserved pathway that serves as a critical regulator of cell fate. From a series of studies, including a report in this issue, researchers have begun to elucidate the critical functions of Notch signaling in the regulation of melanocyte lineage development. With evidence of a recently identified role for Notch signaling in melanomagenesis, characterization of downstream molecular events may offer potential avenues for the development of novel therapeutic strategies.     

A review of genetic disorders of hypopigmentation: lessons learned from the biology of melanocytes

Abstract:  Inherited diseases of pigmentation were among the first traits studied in humans because of their easy recognition. The discovery of genes that regulate melanocytic development and function and the identification of disease-causative mutations have greatly improved our understanding of the molecular basis of pigmentary genodermatoses and their underlying pathogenetic mechanisms. Pigmentation mutants can account for hypo-/amelanosis, with or without altered melanocyte number, resulting in different phenotypes, such as Waardenburg syndrome, piebaldism, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, oculocutaneous albinism and Griscelli syndrome. In this review, we summarize the basic concepts of melanocyte biology and discuss how molecular defects in melanocyte development and function can result in the development of hypopigmentary hereditary skin diseases.     

Ocular manifestations of pigmentary disorders.

Disorders of pigmentation can result from either an abnormal number of melanocytes, as in nevus of Ota and vitiligo, or an abnormal amount of melanin production, as in albinism. Melanin-producing cells are found in the skin, mucous membranes, uveal tract, and retinal pigment epithelium of the eye and the stria vascularis of the inner ear. Thus, many of the hereditary or congenital pigmentary disorders of the skin are associated with similar pigmentary abnormalities in the eye, such as iris heterochromia or changes in pigmentation of the fundus; however, more commonly, the associated eye finding is a defect in ocular motility, i.e., strabismus and nystagmus, suggesting a concomitant defect in neurologic development. In albinos, the observed neurologic abnormality in the visual pathway and foveal hypoplasia are hypothesized to be related directly to the lack of melanin in the pigment epithelium during development. In acquired disorders of pigmentation, in particular, vitiligo, Vogt-Koyanagi-Harada syndrome, and onchocerciasis, there is a frequent association with uveitis, suggesting an inflammatory cause for the cutaneous pigmentary changes.     

Normal and abnormal human skin colour: from research to aesthetics

Skin color is controlled by pigmentary genes that regulate constitutive skin pigmentation and by environmental factors, the most obvious of them being solar U.V. At this time, more than 125 distinct pigmentary genes are known. They affect embryogenesis and survival of the melanocyte system, mélanosome biogenesis, melanogenesis, mélanosome transport and transfer, eumelanins/pheomelanins ratio and epidermal mélanosome turn-over and elimination. The pigmentary disorders of the skin are common and represent an important part of dermatologist activity. They concern at the same time the general dermatology and the aesthetic dermatology.     

Genetisch bedingte Pigmentstörungen

Pigmentation in human skin differs individually and is regulated by more than 100 genes. The discovery of an increasing number of these genes has shed light on the molecular basis and pathogenesis of genetic pigmentary disorders. They are very rare and can be caused by changes in melanocyte number or melanin synthesis as well as development, transport and transfer of melanosomes. Pigmentary disorders can be divided into hyper- and hypopigmentation, of which the distribution can be diffuse or localized. Localized hypopigmentation can be found in piebaldism, Waardenburg syndrome and Tietz syndrome, whereas diffuse forms are typical for oculocutaneous albinism, Hermansky-Pudlak syndrome, Chediak-Higashi syndrome and Griscelli syndrome. Hyperpigmentation can be divided into diffuse, reticular or localized forms. They must be distinguished from endocrinopathies which may show hyperpigmentation, and from poikilodermatous syndromes displaying internal involvement.     

243例太田痣临床分析

目的 对湖北及周边地区太田痣患者进行临床分析.方法 回顾分析243例太田痣患者在发病时间、色素性疾病家族史及患者母亲妊娠期间是否有用药史等方面进行统计学比较.结果 太田痣出生时发病者占58.0%,出生后发病者占42.0%,主要集中于5～15岁.有色素性疾病家族史者占60.1%,其中以雀斑和咖啡斑为主.患有太田痣与女性妊娠期间是否有用药史无明显关系.结论 太田痣可能具有遗传性,具有色素性疾病史的患者,其后代患太田痣的可能性较大.