Notch信号通路在遗传性色素障碍性皮肤病的研究进展

色素障碍性皮肤病主要由黑素细胞功能障碍或数目异常所致,严重影响皮肤外观.近期一系列研究报道,Notch信号通路组成部分功能的异常或缺失与人类遗传性色素障碍性皮肤疾病发病相关.Notch信号通路是一条高度保守的调控细胞分化增殖凋亡的信号传导途径,但其如何导致色素异常的致病机制尚不明确.探讨Notch信号通路在遗传性色素障碍性皮肤病的研究进展,为理解遗传因素在黑素细胞生长发育和功能中发挥的作用提供了新视野.     

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     

皮肤病中c-Jun氨基末端蛋白激酶通路的研究现况

c-Jun氨基末端蛋白激酶是丝裂原活化蛋白激酶家族的成员,调节细胞的生长、发育、增殖和分化.c-Jun氨基末端蛋白激酶的异常表达与人皮肤疾病的发生、发展密切相关.研究证实,c-Jun氨基末端蛋白激酶在多种皮肤疾病患者的真/表皮中表达过度增高及异常活化,进而导致细胞的生长、发育、增殖、分化异常以及炎症反应和细胞凋亡的发生.选择阻断c-Jun氨基末端蛋白激酶通路的异常活化可以使病情得到改善.针对c-Jun氨基末端蛋白激酶信号通路的靶向治疗已经成为目前多种皮肤病的研究热点.     

Nrf2信号通路及其在皮肤病中的应用进展

Nrf2信号通路是缓解细胞氧化应激损伤时最重要的抗氧化应激通路,其转录激活过程是整个氧化应激过程关键步骤,在抵抗外界氧化应激损伤过程中维持体内氧化还原平衡,提高细胞抗氧化应激能力中发挥重要作用。本文将概述Nrf2信号通路在皮肤病中的应用和研究进展。     

Notch1信号途径在皮肤鳞癌SCL-1细胞中的激活及其对细胞周期的影响

目的:研究Notch1及其下游靶基因Hes1在皮肤鳞状细胞癌(简称鳞癌)细胞株SCL-1细胞中的表达及上调Notch1表达对细胞周期的影响.方法:将Notch1真核表达载体通过脂质体2000转染SCL-1细胞,通过反转录(RT)-PCR和Western blotting检测Notch1和Hes1基因在皮肤鳞癌SCL-1细胞中的表达,并利用CCK-8试剂分析上调Notch1表达对皮肤鳞癌SCL-1细胞增殖的影响,通过流式细胞仪观察Notch1过表达对细胞周期的影响.结果:SCL-1细胞中存在Notch1和Hes1基因表达,提示该信号途径在皮肤鳞癌细胞中处于激活状态,转染Notch1真核表达载体后,与未处理组和空载体组相比,转染组中Nowh1和Hes1的mRNA和蛋白表达都明显增加(P<0.05).此外,细胞增殖实验结果表明,过表达Notch1能明显抑制皮肤鳞癌SCL-1细胞增殖.流式细胞仪检测结果显示,Notch1过表达使细胞周期静止在G0/G1期.结论:Notch1过表达能引起皮肤鳞癌SCL-1细胞的细胞周期静止在G0/G1期,Notch1信号途径可能在皮肤鳞癌的进展中起作用.     

与紫外线致皮肤损伤相关的部分信号通路研究进展

紫外线照射可使皮肤损伤,导致皮肤光老化或皮肤肿瘤.多个信号通路如Nrf2-Keap1-ARE、核因子κB、丝裂原活化蛋白激酶(MAPK)、磷脂酰肌醇-3激酶-丝氨酸/苏氨酸激酶-西罗莫司靶蛋白(PI3K-AKt-mTOR)信号通路等参与皮肤光老化和(或)皮肤肿瘤的发病.Nrf2信号通路在氧化应激状态下开启,有维持氧化还原平衡和参与细胞新陈代谢等作用.核因子κB信号通路的激活引起基质金属蛋白酶等水平上调,与皮肤老化和非黑素性皮肤癌有关.MAPK信号通路参与皮肤老化和皮肤肿瘤的进展.PI3K-AKt-mTOR信号通路主要与皮肤肿瘤相关.紫外线照射可诱导上述通路的活化,参与皮肤光老化或皮肤肿瘤的发生发展.对上述通路的进一步研究有望为抵御皮肤的光老化和皮肤肿瘤提供新的方法.     

蛋白激酶JNK、p38与皮肤病

c Jun氨基末端激酶、p38是丝裂原活化蛋白激酶细胞信号转导通路中重要的蛋白激酶。在炎性细胞因子和应激环境的刺激下 ,可导致c Jun氨基末端激酶通路与p38通路的激活 ,并进而改变细胞的生物学特性。近年来发现c Jun氨基末端激酶、p38丝裂原活化蛋白激酶通路在多种皮肤病中高度激活 ,并提示与发病机制有一定关联 ,如单纯疱疹、HIV感染、HPV感染以及皮肤肿瘤等。     

紫外线治疗皮肤病的新进展

紫外线是治疗皮肤病的重要手段,其中311rnm～313 nm的窄谱中波紫外线与340 nm～400 nm的长波紫外线对某些皮肤病有独特的疗效,可治疗特应性皮炎、白癜风、银屑病、硬皮病、皮肤T细胞淋巴瘤及其他难治性皮肤病,疗效确切.     

真皮树突状细胞与皮肤病

真皮树突状细胞是一类抗原递呈细胞 ,存在于正常皮肤和某些皮肤病真皮中。在不同皮肤病中 ,真皮树突状细胞的种类、表型特点、表达数量与方式都各不相同。近年来 ,不断发现新的表型真皮树突状细胞如FXⅢa+ 真皮树突状细胞、CD3 4 + 真皮树突状细胞、Thy1 + 真皮树突状细胞、促生长素抑制素真皮树突状细胞、凝血调节蛋白真皮树突状细胞等。它们存在于皮炎、银屑病、皮肤肿瘤等皮肤病真皮中 ,影响着疾病的发生和发展。对真皮树突状细胞的研究有助于对某些皮肤病机理的了解 ,对真皮树突状细胞的监测和调节可能为一些慢性顽固性皮肤疾病的治疗提供新的方法。     

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.     

Notch signaling: its role in epidermal homeostasis and in the pathogenesis of skin diseases

Skin undergoes self-renewal throughout life. Terminally differentiated keratinocytes, namely the corneocytes, are continually shed from the surface of the skin, whereas immature cells produce progeny that proceed through the differentiation process. Notch signaling controls a number of cellular processes including cell fate decision, proliferation, differentiation and survival/apoptosis. Hence, Notch and its ligands are expressed in multiple tissues including the skin, where they are abundantly expressed in the epidermis. Notch activation results in the promotion of growth arrest and the onset of differentiation, therefore suggesting that specific Notch activation may regulate skin homeostasis by balancing these processes, i.e. Notch signaling functions as a molecular switch that controls the transition of cells between skin layers during the epidermal differentiation process. Recent advances in the study of Notch signaling have confirmed that there is cross-talk between the Notch signaling pathway and a variety of other signaling molecules including Sonic hedgehog (Shh), beta-catenin and the p53 family member, p63. The absence of Notch activity allows Wnt and Shh signaling to persist in a tissue where they are normally repressed. In addition, Notch counteracts the action of p63 to maintain immature cell characteristics. However, aberrant Notch signaling results in the development of psoriasis and skin cancers such as squamous cell carcinoma, basal cell carcinoma and malignant melanoma. Future efforts to further define how Notch controls cell proliferation and differentiation may lead to the application of Notch in new therapies for various skin diseases.     

Janus激酶抑制剂在皮肤病治疗中的应用前景

【摘要】 Janus激酶（JAK）和信号转导和转录激活因子（STAT）所构成的JAK-STAT信号通路是一条重要的细胞内信号通路，参与许多炎症性疾病的发病。JAK抑制剂阻断该通路已经成为治疗某些疾病的有效方法，例如类风湿关节炎、溃疡性结肠炎。然而，目前JAK抑制剂尚未被批准应用于皮肤病治疗。本文就JAK抑制剂在皮肤疾病中的应用前景进行综述。     

Notch Intracellular Domain Expression in Various Skin Fibroproliferative Diseases

Background

The effects of the Notch signaling pathway in fibroproliferative skin diseases have not been fully elucidated.

Objective

The aim of this study was to investigate the expression of activated Notch signaling molecules in various skin fibroproliferative diseases.

Methods

Immunohistochemical analysis of Notch intracellular domain (NICD) expression in keloid, hypertrophic scar, morphea, dermatofibroma, and normal control skin specimens was performed, and the clinical characteristics of patients with various skin fibroproliferative diseases were analyzed.

Results

NICD was highly expressed in fibroblasts of keloids and moderately to highly expressed in hypertrophic scars and dermatofibromas, whereas low or no expression was detected in the fibroblasts of normal skin specimens and morpheas. NICD was constitutively expressed in keratinocytes, endothelial cells, and immune cells in normal skin specimens.

Conclusion

NICD was significantly expressed in human fibroproliferative skin disorders, especially keloids, suggesting that an activated Notch signaling pathway is involved in the pathogenesis of skin fibrosis.     

Nitric oxide and its implications in skin homeostasis and disease – a review

Abstract The recent identification of the nitric oxide synthase (NOS) pathway in various cell types in the skin has provided important insight into the molecular mechanisms underlying regulatory and homeostatic functions of the skin. Many studies also point to perturbations or defects in the signaling cascade of nitric oxide (NO) and reactive nitrogen intermediates as key players in skin disease pathogenesis. A critical role for NO is now established for a subset of human skin diseases, and new mechanism-based therapies may be available in the near future. This remarkable progress and the implications it may have for common forms of skin disease are reviewed here. Received: 22 June 1998 / Accepted: 31 August 1998     

存活素和皮肤病

存活素是凋亡抑制蛋白家族的新成员,不仅具有抑制细胞凋亡的能力,而且参与细胞有丝分裂和胞质分离的调节。存活素仅表达于各种皮肤良恶性病变,而不表达于正常皮肤。综述存活素分子结构、抑制凋亡的机制、在细胞分裂中的作用、与各种良恶性增生性皮肤病的关系以及靶向治疗。     

调节T细胞及其在皮肤病中的作用

调节T细胞是一类具有免疫抑制作用的细胞群，通过细胞接触抑制或抑制性细胞因子主动抑制自身免疫性T细胞。对于维持机体免疫自稳、预防自身免疫病具有极其重要的作用。最近研究表明，调节T细胞与银屑病、系统性红斑狼疮等自身免疫性皮肤病和皮肤肿瘤的发病存在相关性．综述了调节T细胞在这些皮肤病的发病机制中的作用。     

基底细胞癌中肿瘤相关信号通路研究进展

肿瘤的发生、发展、浸润以及转移中均伴随着相关信号通路的信号失调.基底细胞癌是一种最为常见的皮肤恶性肿瘤.大量的研究发现,以Hedgehog信号通路为核心包括wnt、表皮生长因子受体、Notch、转化生长因子β/骨形态发生蛋白、FasL-Fas、P13K-AKT、促分裂原活化蛋白激酶和核因子-κB等多种信号通路的失调在其肿瘤生物学行为中发挥着重要的作用.更为重要的是,基底细胞癌中Hedgehog信号通路在信号传导途径中与包括wnt、表皮生长因子受体、转化生长因子β/骨形态发生蛋白和Notch等信号通路存在着交联机制.这些信号通路的研究对于更加深入地揭示基底细胞癌的肿瘤发生发展机制及寻找更加准确的药物治疗靶点具有重要的意义.

Abstract：

Deregulation of signaling pathways is commonly accompanied with the initiation, development,infiltration and metastasis of many kinds of tumors.Basal cell carcinoma(BCC)is a most common form of skin malignancy.Numerous studies have shown that many signaling pathways including Wnt, epidermal growth factor receptor(EGFR), Notch, transforming growth factor(TGF)β/bone morphogenetic protein(BMP), FasL-Fas, PI3K-AKT, mitogen-activated protein kinase(MAPK), nuclear factor kappa B, etc, play an essential role in the biological behaviors of BCC.Of these signaling pathways, Hedgehog is the core pathway.Most importantly, there are some cross-talks between Hedgehog pathway and Wnt, EGFR, TGFβ/BMP, Notch pathway in the signal transduction in BCC.Researches on these signaling pathways in BCC may contribute to the illumination of pathogenesis of BCC and searches for accurate therapeutic targets.