内皮素与多种皮肤病

内皮素（ET）家族包括三种异构肽：ET-1，ET-2，ET-3，广泛分布于人体多种组织器官。内皮素与受体结合后产生广泛的生物学效应，如促进细胞增殖、组织纤维化等，参与皮肤肿瘤、红斑鳞屑病、结缔组织病等多种皮肤病的发生。进一步研究内皮素及其受体在皮肤病中的作用，将可能揭示某些疾病的发病机制并为之带来新的疗法。     

皮肤与系统性疾病 (一)皮肤与系统性疾病的联系

人体是一个十分复杂的整体,各种生理活动既对立又统一。皮肤和其他脏器组织之间有密切的联系,各脏器的病变和全身性疾病可在皮肤上反映出不同的征候。因此在临床医疗工作中遇到的很多皮肤病常是系统性疾病的一种表现。此外,有些皮肤病可引起其他脏器功能紊乱或病变。熟悉皮肤和系统性疾病间的相互关系,对了解皮肤病的病因和病理生理以及全身性疾病的及时诊断、治疗和预后都有极其重要的意义。     

内源性大麻素系统与炎症性皮肤病

内源性大麻素系统包括内源性大麻素受体和内源性大麻素以及一系列参与内源性大麻素系统生物合成和代谢的酶类以及膜转运受体.近年来,在角质形成细胞、皮肤成纤维细胞、皮脂腺细胞等多种皮肤细胞中发现了具有生物学效应的内源性大麻素系统.越来越多的研究发现,内源性大麻素系统参与正常皮肤生理生化活动和炎症反应,并在多种炎症性皮肤病中起作用.目前内源性大麻素系统的临床应用尚不成熟,但内源性大麻素系统的研究为临床炎症性皮肤病的治疗提供了新视角和新策略.     

性激素受体与皮肤病

皮肤及其附属器是性激素的靶器官之一，存在三种性激素受体，它们介导性激素调节皮肤组织、细胞的增殖分化。性激素受体数量和功能状态的改变与某些皮肤病的病理生理密切相关。对皮肤病性激素受体的检测在探讨皮肤病的病理生理、诊断治疗及预后估计中具有重要意义。     

一氧化氮与皮肤

一氧化氮作为一种多效性生物调节分子日益受到人们的重视，它可在机体多种细胞中合成，并在多种生理和病理过程中起到重要作用，近年研究表明，皮肤组织中一些细胞亦能原生和被诱导合成一氧化氮，一氧化氮在皮肤生理和病理过程中的具体作用尚不明，但已有证明表明，它可能参与皮肤血液循环，抗感染，组织修复，免疫和炎症反应等诸多方面的调节，并可能与某些皮肤病的发生发展有密切联系。     

内皮素与多种皮肤病

内皮素(ET)家族包括三种异构肽:ET-1,ET-2,ET-3,广泛分布于人体多种组织器官.内皮素与受体结合后产生广泛的生物学效应,如促进细胞增殖、组织纤维化等,参与皮肤肿瘤、红斑鳞屑病、结缔组织病等多种皮肤病的发生.进一步研究内皮素及其受体在皮肤病中的作用,将可能揭示某些疾病的发病机制并为之带来新的疗法.     

HaCaT细胞蛋白质组双向凝胶电泳技术的初步建立

皮肤是人体最大的器官,蛋白质组学研究能够动态、整体、定量地考察皮肤各种生理、病理发生过程中蛋白质种类、数量的改变,有助于研究者探讨皮肤病发病机理,寻找皮肤病诊断和预后的特异性标志,以及药物治疗的靶标.     

神经肽与皮肤免疫和炎症

皮肤组织中存在多种神经肽，来源于神经系统，有的可产生于局部细胞。它们可通过一系列作用影响和调节皮肤免疫和炎症包括调节白细胞迁移、粘附分子表达，细胞因子产生，辅佐细胞抗原提呈，影响微血管通透性和皮肤细胞的生长、增殖等。神经肽可能借助这些效应参与一些皮肤病病理生理的过程。     

皮肤病中蛋白激酶D1研究进展

蛋白激酶D1是一种在体内多个重要器官广泛表达的钙离子/钙调蛋白依赖性的丝氨酸/苏氨酸蛋白激酶,参与多种重要的生理和病理活动,在许多肿瘤组织中表达异常。PKD1促进角质形成细胞增殖,抑制其分化,对表皮伤口愈合及肿瘤的形成具有促进作用,与UVB、ROS等影响皮肤疾病发生发展的重要因素之间都有密切联系。因此PKD1可能成为治疗某些皮肤病甚至皮肤肿瘤更有效的分子靶点。     

干细胞在皮肤病中的应用

干细胞是存在于所有多细胞组织中,具有自我更新、增殖分化潜能的一种未分化细胞。干细胞的种类随研究的深入逐渐增多。干细胞治疗相关疾病的具体机制多数未明。目前在皮肤科领域,干细胞研究主要集中于皮肤损伤修复与组织工程学再生以及自身免疫相关性疾病、遗传性皮肤病、皮肤自然衰老与光老化、皮肤肿瘤等疾病治疗方面。干细胞应用的适应证随着研究的深入逐渐增加,特别在目前传统治疗方法棘手的自身免疫疾病、遗传性皮肤病、皮肤肿瘤等领域显示出优势。     

3D生物打印技术在皮肤科的研究进展

3D打印技术是基于计算机三维数字成像技术及多层次连续打印的一种新型数字化成型技术.3D生物打印技术则是在3D打印的基础上,以活细胞为原料打印活体组织的一种技术,近年来其在临床中的应用越来越广泛,已应用于皮肤、骨骼、血管、心脏组织等的体外再生与重建.目前,许多皮肤病如白癜风、银屑病等治疗比较困难,此类疾病是皮肤科领域研究的热点和难点.而3D生物打印技术可用于皮肤病的研究、皮肤创面修复等,为皮肤病患者带来了曙光.     

Cadherins in Cutaneous Biology

The role of cadherins in cutaneous biology has focused mainly on the classical cadherins, E- and P-cadherin. In this review, roles for cadherins in skin morphogenesis, keratinocyte differentiation, and cancer metastasis are discussed. E-cadherin is expressed on the surfaces of whole epidermal layer cells, and P-cadherin is expressed only on the surfaces of basal cells. Ultrastructural studies have shown that E-cadherin is distributed on the cytoplasmic membranes of keratinocytes with a condensation in the intercellular space of the desmosomes. During human skin development, P-cadherin expression is spatiotemporally controlled and closely related to the segregation of basal layers as well as to the arrangement of epidermal cells into eccrine ducts. In human skin diseases, E-cadherin expression is markedly reduced on the acantholytic cells of tissues in pemphigus and also in Darier's disease. Keratinocytes cultured in high calcium produce a much more intense immunofluorescence of intercellular E- and P-cadherin than do cells grown in low calcium. Ultrastructural studies show that E-cadherin on the cytoplasmic membrane of the keratinocytes is shifted to desmosomes under physiological conditions and therein expresses an adhesion function is association with other desmosomal cadherins. Cell adhesion molecules are now considered to play significant roles in the cellular connections of cancers and metastatic cells. Reduced expression of E-cadherin on invasive neoplastic cells has been demonstrated for cancers of the stomach, liver, breast, and several other organs. This reduced expression of E-cadherin is observed in squamous cell carcinoma and Paget's disease. Soluble E-cadherins in sera are elevated in various skin diseases, including bullous pemphigoid, pemphigus vulgaris and psoriasis, but not in patients with burns. Markedly high levels in soluble E-cadherin are demonstrated in patients with metastatic cancers.     

Heat shock proteins (HSP): dermatological implications and perspectives

In recent years, several studies have demonstrated the protective effect of Heat Shock Proteins (HSP) on different organs and tissues under stressful conditions. However, most research explores the performance of those molecular chaperones during immune responses or pathological conditions like cancer, whereas the number of studies related to the performance of HSPs in the skin during diverse natural or physiopathological conditions is very low. Therefore, the aim of this article was to summarize the main concepts concerning the expression and performance of HSPs, from analysis of current medicine and cosmetics publications, as well as exploring the importance of these proteins in the dermatological area in physiological events such as cutaneous aging, skin cancer and wound healing and to present final considerations related to biotechnology performance in this area.     

The functional relevance of polyploidization in the skin

Cell proliferation and differentiation are tightly coupled through the regulation of the cell division cycle. To preserve specific functional properties in differentiated cells, distinct variants of the basic mitotic cell cycle are used in various mammalian tissues, leading to the formation of polyploid cells. In this issue of Experimental Dermatology, Gandarillas and Freije discuss the evidences for polyploidization in keratinocytes, a process whose physiological relevance is now becoming evident. A better evaluation of these unconventional cell cycles is required not only to improve our understanding of the development and structure of the epidermis but also for future therapies against skin diseases.     

Sphingosine‐1‐phosphate modulators in inflammatory skin diseases – lining up for clinical translation

The bioactive lysophospholipid sphingosine‐1‐phosphate (S1P) is best known for its activity as T‐cell‐active chemoattractant regulating the egress of T cells from the lymph node and, consequently, the availability of T cells for migration into peripheral tissues. This physiological role of S1P is exploited by the drug fingolimod, a first‐line therapy for multiple sclerosis, which “detains” T cells in the lymph nodes. In recent year, it has been elucidated that S1P exerts regulatory functions far beyond T‐cell egress from the lymph node. Thus, it additionally regulates, among others, homing of several immune cell populations into peripheral tissues under inflammatory conditions. In addition, evidence, mostly derived from mouse models, has accumulated that S1P may be involved in the pathogenesis of several inflammatory skin disorder and that S1P receptor modulators applied topically are effective in treating skin diseases. These recent developments highlight the pharmacological modulation of the S1P/S1P receptor system as a potential new therapeutic strategy for a plethora of inflammatory skin diseases. The impact of S1P receptor modulation on inflammatory skin diseases next requires testing in human patients.     

皮肤病相关MicroRNAs表达的研究进展

MicroRNAs(miRNAs)是一种大小约18～25个核苷酸的非编码单链小RNA分子,参与包括细胞增殖、分化、凋亡、发育和逆境应答等多种生物学过程。近年来研究发现多种miRNA在皮肤生理生化免疫等过程中发挥了极其重要的作用,在某些皮肤病皮损组织中有异常表达,是皮肤病发生、发展过程中重要的调控因素。本文综述miRNAs的生物合成、作用机制、与皮肤病的相关性及研究前景,有助于进一步了解某些皮肤病的病理生理机制,为开展皮肤病miRNAs的表达及功能研究提供线索,为皮肤病早期诊断和治疗提供新的思路。     

Skin bioengineering: preclinical and clinical applications

Regenerative Medicine is an emerging field that combines basic research and clinical observations in order to identify the elements required to replace damaged tissues and organs in vivo and to stimulate the body's intrinsic regenerative capacity. Great benefits are expected in this field as researchers take advantage of the potential regenerative properties of both embryonic and adult stem cells, and more recently, of induced pluripotent stem cells. Bioengineered skin emerged mainly in response to a critical need for early permanent coverage of extensive burns. Later this technology was also applied to the treatment of chronic ulcers. Our group has established a humanized mouse model of skin grafting that involves the use of bioengineered human skin in immunodeficient mice. This model is suitable for the study of physiologic and pathologic cutaneous processes and the evaluation of treatment strategies for skin diseases, including protocols for gene and cell therapy and tissue engineering.     

闭合蛋白表达异常与相关皮肤病

皮肤屏障由角质层、细胞间质和紧密连接组成.闭合蛋白是构成紧密连接的主要蛋白之一,存在于哺乳动物的皮肤、脑、神经系统和内脏组织中,在生理状态下影响紧密连接的整体性及其功能,是构成皮肤栅栏和屏障的主要功能蛋白之一.在人类组织中已发现27种闭合蛋白亚型,在上皮细胞间形成对电解质及溶质分子的屏障结构.研究表明,皮肤屏障功能受损是多种皮肤病如银屑病、特应性皮炎、家族性良性天疱疮、光线性角化病等重要的发病因素,这与闭合蛋白功能和结构的异常密切相关.闭合蛋白家族中不同成员在不同皮肤病中的表达各异.     

Regenerative medicine in dermatology: biomaterials,tissue engineering,stem cells,gene transfer and beyond

Please cite this paper as: Regenerative medicine in dermatology: biomaterials, tissue engineering, stem cells, gene transfer and beyond. Experimental Dermatology 2010; 19 : 697–706. Abstract: The term ‘regenerative medicine’ refers to a new and expanding field in biomedical research that focuses on the development of innovative therapies allowing the body to replace, restore and regenerate damaged or diseased cells, tissues and organs. It combines several technological approaches including the use of soluble molecules, biomaterials, tissue engineering, gene therapy, stem cell transplantation and the reprogramming of cell and tissue types. Because of its easy accessibility, skin is becoming an attractive model organ for regenerative medicine. Here, we review recent developments in regenerative medicine and their potential relevance for dermatology with a particular emphasis on biomaterials, tissue engineering, skin substitutes and stem cell‐based therapies for skin reconstitution in patients suffering from chronic wounds and extensive burns.     

pH in nature,humans and skin

The pH plays an important physiological role in nature and humans. pH varies from 1 to 8 in human organs with tight regulation in blood and epithelia of barrier organs. The physiological pH of the stratum corneum is 4.1–5.8 and several mechanisms contribute to its formation: filaggrin degradation, fatty acid content, sodium‐hydrogen exchanger (NHE1) activation and melanosome release. First, the acidic pH of the stratum corneum was considered to present an antimicrobial barrier preventing colonization (e.g. by Staphylococcus aureus and Malassezia). Later on, it was found that the pH influences skin barrier function, lipid synthesis and aggregation, epidermal differentiation and desquamation. Enzymes of ceramide metabolism (e.g. β‐glucocerebrosidase or acid sphingomyelinase) as well as proteases (e.g. chymotryptic enzyme or cathepsin D linked to epidermal differentiation and desquamation) are regulated by the pH. Experimental disruption of the physical barrier leads to an increase of pH, returning to normal levels only after many hours. Inflammatory skin diseases and diseases with an involvement of the epidermis exhibit a disturbed skin barrier and an increased pH. This is known for atopic dermatitis, irritant contact dermatitis, ichthyosis, rosacea and acne, but also for aged and dry skin. Normalizing the pH by acidification through topical treatment helps to establish a physiological microbiota, to repair skin barrier, to induce epidermal differentiation and to reduce inflammation.