角质形成细胞在银屑病发病机制中的研究进展

银屑病的病因不清,但角质形成细胞功能改变具有重要作用。本文综述了近几年有关角质形成细胞增殖和分化调节异常、分泌细胞因子和粘附分子的改变及其与Ｔ细胞的相互作用等方面在银屑病的发病机制中作用的研究进展。     

瘢痕疙瘩发病机制研究的新进展

瘢痕疙瘩的发病机制参与因素众多，目前并未完全清楚，本文将近几年来国内外在细胞因子、细胞凋亡、细胞外基质及角质形成细胞的作用等方面有关研究的最新进展进行了报告和分析，希望能为下一步研究和治疗提供一些启示。     

角质形成细胞中的信号转导

角质形成细胞是使皮肤保持稳态和参与皮肤病理生理过程的主要细胞。其增殖和分化受许多生物因子控制 ,对胞外信号反应的主要机制———蛋白磷酸化理论也在不断发展。就角质形成细胞信号转导的特点作一概述。     

角质形成细胞在银屑病发病机制中的研究进展

银屑病的病因不清 ,但角质形成细胞功能改变具有重要作用。本文综述了近几年有关角质形成细胞增殖和分化调节异常、分泌细胞因子和粘附分子的改变及其与T细胞的相互作用等方面在银屑病的发病机制中作用的研究进展。     

MMP-2在瘢痕疙瘩侵袭中的作用研究进展

瘢痕疙瘩是一种常见的皮肤病,基质金属蛋白酶-2（MMP-2）作为调节细胞外基质平衡的主要酶,在瘢痕疙瘩的发病尤其是侵袭生长中起着重要作用,其机制可能是通过降解胶原束边缘的细胞外基质而使成纤维细胞向周围正常组织侵袭。     

角质形成细胞生长因子与银屑病的关系

角质形成细胞生长因子是近年来发现的有着重要生物功能的生长因子,它属于成纤维细胞生长因子家族,由成纤维细胞产生。角质形成细胞生长因子可刺激角质形成细胞的增生、分化、移行,促进上皮细胞的再生、增厚,对银屑病的发病机制及其治疗可能有一定的启示。本文就角质形成细胞生长长因子和的生物学功能及其与角质形成细胞及银屑病的关系做一定综述。     

EMT在瘢痕疙瘩中的作用研究进展

上皮间质转化(epithelial-to-mesenchymal transition,EMT)是上皮细胞极性丧失且发展为具有迁移和侵袭特性的间充质细胞的动态过程.EMT已被证实与伤口愈合、器官纤维化及癌症发展有关.瘢痕疙瘩的研究都专注于瘢痕疙瘩成纤维细胞,近几年来广大学者们开始注重瘢痕疙瘩角化上皮细胞侵袭周围正常皮肤...     

角质形成细胞生长因子与银屑病的关系

角质形成细胞生长因子是近年来发现的有着重要生物学功能的生长因子 ,它属于成纤维细胞生长因子家族 ,由成纤维细胞产生。角质形成细胞生长因子可刺激角质形成细胞的增生、分化、移行 ,促进上皮细胞的再生、增厚 ,对银屑病的发病机制及其治疗可能有一定的启示。本文就角质形成细胞生长因子的生物学功能及其与角质形成细胞及银屑病的关系做一综述。     

与角质形成细胞相关自身抗体的研究进展

近年来 ,随着分子生物学和分子免疫学的发展 ,人们发现许多皮肤病和针对角质形成细胞的自身抗体有着密切的联系。这类抗体对疾病的诊断 ,治疗有所帮助。大致可分为抗核抗体、抗胞浆抗体及抗胞膜抗体三种类型。     

Conditioned medium from keloid keratinocyte/keloid fibroblast coculture induces contraction of fibroblast-populated collagen lattices

BACKGROUND: Keloid scars represent a pathological response to cutaneous injury. Overproliferation of fibroblasts and overproduction of collagen characterize these abnormal scars. The pathology of these scars remains poorly understood. The role of epithelial-mesenchymal interactions in keloid pathogenesis and scar contracture has recently been explored. OBJECTIVES: To test our hypothesis that epithelial-mesenchymal interactions play a major role in modulating keloid scar contracture. METHODS: A coculture model was employed wherein keloid and normal keratinocytes were cocultured with keloid or normal fibroblasts, and the conditioned media from day 5 cocultures were collected to study the effect of the paracrine secretions on contraction of an in vitro fibroblast-populated collagen lattice (FPCL) model. RESULTS: Keloid keratinocyte/keloid fibroblast coculture conditioned media brought about increased contraction of the collagen lattice compared with non-cocultured conditioned media. When keloid fibroblasts populated the collagen lattice, significantly increased lattice contraction was induced compared with lattices populated by normal fibroblasts. The addition of antitransforming growth factor (TGF)-beta neutralizing antibody to the conditioned media produced an attenuation of the contraction of the FPCLs. When keloid and normal fibroblasts were cultured on chamber slides and treated with conditioned media from coculture and non-coculture series, immunohistochemical analysis demonstrated an increased expression of alpha-smooth muscle actin (a marker for fibroblast differentiation into myofibroblasts) in fibroblasts exposed to conditioned media from coculture. CONCLUSIONS: These data indicate that epithelial-mesenchymal interactions are likely to play a major role in scar contracture and scar pathogenesis, and underscore the role of TGF-beta1 as a key player in keloid pathogenesis.     

The role of R-spondin2 in keratinocyte proliferation and epidermal thickening in keloid scarring

Keloids are found only in humans and the underlying biochemical mechanisms of their pathogenesis remain unknown. R-spondins (Rspos) are a relatively new group of secreted proteins known to be Wnt/β-catenin signaling agonists, but their role in keloids has yet to be elucidated. We investigated the expression levels of R-spondin2 (Rspo2) in cell lysates and conditioned media of monocultures and co-cultures of fibroblasts and keratinocytes derived from keloids and normal skin. In this study we found increased protein expression and secretion of Rspo2 in respective monocultures of keloid fibroblasts and keratinocytes when compared with their normal counterparts. Double-chamber co-culture experiments implicated the role of keloid keratinocytes (KKs) in the induction of Rspo2 secretion from fibroblasts because of epithelial-mesenchymal interactions. Addition of recombinant human Rspo2 in culture increased the proliferation of keratinocytes and it acted synergistically with Wnt3a through the canonical Wnt/β-catenin pathway. Overexpression of Rspo2 in normal fibroblasts brought about thicker epidermis when compared with control fibroblasts in a skin organotypic culture model. This observation coincides with the hyperproliferative phenotype of thickened epidermis seen in keloids. Taken together, the results suggest the possible double paracrine action of KKs in inducing higher expression of Rspo2 in fibroblasts that promotes keratinocyte proliferation and epidermal thickening.     

几丁糖对瘢痕疙瘩成纤维细胞形态及增殖的作用

目的：探讨几丁糖对瘢痕疙瘩成纤维细胞形态及生长增殖的作用，为临床应用几丁糖治疗瘢痕疙瘩提供理论基础：方法：用组织块法进行瘢痕疙瘩、正常皮肤成纤维细胞的体外培养；用光学显微镜和电子显做镜观察细胞的形态结构；用四甲基偶氮唑蓝(MTT)比色法和流式细胞仪检测不同浓度几丁糖对不同来源的成纤维细胞生长增殖和细胞周期的影响．结果：随着几丁糖浓度的增高，瘢痕疙瘩来源的成纤维细胞细胞器萎缩，4值减小，C0 G1期的细胞百分比增多，S期G2 M期的细胞百分比减少．结论：几丁糖对正常皮肤和瘢痕疙瘩来源的成纤维细胞的生长增殖均有抑制作用，几丁糖可能在瘢痕疙瘩的防治中有一定的作用．     

角质形成细胞生长因子对HaCaT细胞增殖的影响

目的:研究角质形成细胞生长因子(KGF)对HaCaT细胞增殖的影响,探讨KGF与银屑病表皮过度增殖的关系。方法:利用HaCaT细胞体外培养,采用KGF为增殖诱导剂,四甲基偶氮唑盐比色法(MTT)检测不同浓度的KGF对HaCaT细胞增殖率的影响;检测KGF对细胞生长曲线及细胞集落形成的影响。结果:MTT实验表明,KGF可刺激HaCaT细胞增殖,刺激作用呈浓度依赖性(r=0.981,P<0.05);10 ng/mL KGF作用下HaCaT细胞的生长速度较对照组明显加快(P<0.05),集落形成率较对照组增加(P<0.05),且细胞呈明显的增殖形态,形成的集落较大,集落内细胞多呈星状,胞内染色质丰富。结论:KGF具有显著的促HaCaT细胞增殖作用,银屑病皮损区域KGF表达增加可能是引起表皮过度增殖的重要致病因子。     

Sphingosine may have cytotoxic effects via apoptosis on the growth of keloid fibroblasts

Keloids are often resistant to treatment, causing much suffering to the patient. Our previous work found that ceramide (Cer) inhibits growth of fibroblasts via apoptosis. However, when compared to normal fibroblasts (NFs), which are quiescent, keloid fibroblasts (KFs) rapidly proliferate and are reported to be resistant to apoptosis via Cer. Sphingosine (Sph) is a metabolite product of ceramide that has some different biochemical properties. Thereofore, we investigated the cytotoxic effects of Sph on cultured fibroblasts from keloid lesions and normal skin in order to evaluate the possibility of using Sph in the treatment of keloid. We used the lactic dehydrogenase (LDH) method, MTT method, and propidium iodide (PI) method. Sph had cytotoxic effects via apoptosis on both the KFs and NFs. Our results indicate that Sph may be applicable to the future treatment of keloid.     

Immunomodulatory effects of a set of amygdalin analogues on human keratinocyte cells

Peptide T (PT) is an octapeptide shown to resolve psoriatic lesions. Our previous investigations suggest that keratinocytes play an important role in conditioning the therapeutic effects of the PT in psoriasis. However, peptides are not good therapeutic agents, because they exhibit poor absorption, are easily metabolized and are immunogenic. Using computational methods, the natural product amygdalin was identified as peptidomimetic of PT. However, amygdalin exhibits a toxic profile due to its cyanide group. To overcome this deleterious effect, we synthesized analogues lacking the cyanide group. Human keratinocytes were treated with PT or with three different peptidomimetics of PT. To study its effects on the expression of HSP-70, TGF-beta, alpha-v integrin, ICAM-1 and cytokines, we analysed the protein levels by Western blot and ELISA. Our results show that the different peptidomimetics of PT tested exhibit a similar biological behaviour in regard to the overexpression of HSP-70, TGF-beta and alpha-v integrin than the native peptide. TNF-alpha is overexpressed by PT and SVT-03018; between the other two analogs, SVT-03016 do not produce any significant change in regard to the control, while SVT-03017 shows only a moderate increase in regard to control. SVT-03018 provokes a remarkable upregulation of IL-10, stronger than SVT-03016, SVT-03017 and PT. All the other three analogues reduce comparably to the PT, the expression of ICAM-1 and do not increase the release of proinflammatory cytokines. The results highlighted that the three analogues of amygdalin with the cyanide group removed exhibit the same biological effects of PT. Therefore, they can be considered peptidomimetics, suggesting their possible use in the treatment of psoriasis.     

Lupus vulgaris on keloid

A 28-year-old man presented with multicentric lupus vulgaris on keloids over chest, axilla, neck and back for last 6 months. He had pulmonary tuberculosis. All the laboratory investigations were in favour of clinical diagnosis. The patient responded to antituberculosis therapy.     

姜黄油对角质形成细胞体外增殖分化影响的研究

目的：探讨姜黄油对角质形成细胞体外增殖分化的影响。方法：以人角质形成细胞株COLO-16细胞为模型，噻唑盐比色法(MTT)检测细胞活性和生长情况；免疫组化SABC法检测姜黄油对增殖细胞核抗原(PCNA)表达的影响；电镜观察姜黄油对细胞超微结构的影响。结果：姜黄油抑制角质形成细胞增殖，随药物浓度增加，其抑制增殖能力增加，PCNA表达逐渐减弱，且对角质形成细胞超微结构有直接损伤作用。结论：姜黄油具有抑制体外角质形成细胞增殖分化的作用，有望成为一种治疗增殖性皮肤病的外用药物。