细胞因子与病理性瘢痕

病理性瘢痕包括增生性瘢痕和瘢痕疙瘩，其发病机制错综复杂，可能为多因素综合作用的结果。细胞因子在病理性瘢痕的发生、发展过程中扮演了极为重要的角色。大部分细胞因子如转化生长因子-β、结缔组织生长因子、血小板衍化生长因子、胰岛素样生长因子等可促进病理性瘢痕的发生：而某些细胞因子如碱性成纤维细胞生长因子、白介素-1α、前列腺素-E2等则可抑制病理性瘢痕的发生。     

病理性瘢痕成纤维细胞的研究进展

成纤维细胞是瘢痕形成的效应细胞，瘢痕疙瘩和肥厚性瘢痕成纤维细胞存在着广泛的异质性。成纤维细胞原合成增加，降解减少导致病理性瘢痕中胶原过度积聚。成纤维细胞的增殖异常是病理性瘢痕过度增生和持续存在的主要原因。成纤维细胞对细胞因子等因素反应性有明显异常。肥厚性瘢痕的收缩性和成纤维细胞的异质性有直接关系。     

病理性瘢痕成纤维细胞的研究进展

成纤维细胞是瘢痕形成的效应细胞,瘢痕疙瘩和肥厚性瘢痕成纤维细胞存在着广泛的异质性。成纤维细胞胶原合成增加、降解减少导致病理性瘢痕中胶原过度积聚。成纤维细胞的增殖异常是病理性瘢痕过度增生和持续存在的主要原因。成纤维细胞对细胞因子等因素反应性有明显异常。肥厚性瘢痕的收缩性和成纤维细胞的异质性有直接关系。     

促纤维化细胞因子与瘢痕疙瘩

瘢痕疙瘩成纤维细胞是具有独特遗传素质的成纤维细胞亚群，对β－转化生长因子、血小板衍化生长因子、碱性成纤维细胞生长因子、胰岛素样生长因子－Ⅰ、结缔组织生长因子等具有与正常成纤维细胞和增生性瘢痕成纤维细胞不同的反应。这种反应的差异极可能源自相关细胞因子受体水平的改变。     

TGF-β1和MMP-2在病理性瘢痕表皮中的表达和意义

目的:研究TGF-β1和MMP-2在病理性瘢痕表皮中的表达及其意义。方法:运用免疫组化法检测TGF-β1和MMP-2在病理性瘢痕表皮中的表达,并与其在表浅性瘢痕、正常皮肤表皮中的表达进行比较,分析其规律。结果:TGF-β1在病理性瘢痕表皮角质细胞中的阳性率及表达强度均较表浅性瘢痕和正常皮肤明显增高(P值均<0.05),MMP-2在病理性瘢痕表皮中的表达也出现增强,但与表浅性瘢痕、正常皮肤表皮比较,阳性率的差异不具有统计学意义(P>0.05),表达强度间的差异具有统计学意义(P<0.05)。结论:TGF-β1和MMP-2在病理性瘢痕表皮中出现不同程度的表达增高,提示它们可能参与了病理性瘢痕的形成,表皮可能是多种细胞因子的重要来源。     

皮肤肿瘤

20072558细胞因子与病理性瘢痕(综述)/王强(中国医科院皮研所),张国成∥中国麻风皮肤病杂志.-2007,23(2).-147~149病理性瘢痕包括增生性瘢痕和瘢痕疙瘩,其发病机制错综复杂,可能为多因素综合作用的结果。细胞因子在病理性瘢痕的发生、发展过程中扮演了极为重要的角色。大部分细     

自体脂肪注射治疗病理性瘢痕的研究进展

【摘要】 病理性瘢痕一般是各种皮肤创伤后机体异常修复的结果，特征性表现为异常的成纤维细胞增生及细胞外基质沉积。近年来，多项研究证实自体脂肪注射物含有多种可能与治疗瘢痕相关的物质，如基质血管片段、脂肪来源间充质干细胞等，这些物质可通过相关通路抑制成纤维细胞的过度增生和胶原沉积，从而改善病理性瘢痕的进展及预后。临床研究显示，脂肪注射物可以改善病理性瘢痕的厚度、颜色、柔软度和局部症状。更加深入地了解脂肪组织抗纤维化的机制，将有助于病理性瘢痕治疗技术的发展。     

增生性瘢痕的预防与治疗进展

瘢痕是人体创伤修复过程的自然产物,但过度修复将导致病理性瘢痕的形成。增生性瘢痕是常见的病理性瘢痕,引起瘙痒、疼痛、烧灼感和不适,严重影响患者生活。目前可从手术设计、术后应用硅胶膜及注射肉毒素方面预防瘢痕发生,新的治疗方法如局部注射药物、激光治疗及中药治疗等都展现了很好的疗效,有望成为治疗瘢痕的主要选择。本文将结合国内外最新文献对增生性瘢痕防治的进展作一综述。     

促纤维化细胞因子与瘢痕疙瘩

瘢痕疙瘩成纤维细胞是具有独特遗传素质的成纤维细胞亚群 ,对 β 转化生长因子、血小板衍化生长因子、碱性成纤维细胞生长因子、胰岛素样生长因子 Ⅰ、结缔组织生长因子等具有与正常成纤维细胞和增生性瘢痕成纤维细胞不同的反应。这种反应的差异极可能源自相关细胞因子受体水平的改变     

增生性瘢痕和瘢痕疙瘩治疗进展

病理性瘢痕是由创伤等引起.以胶原等大量结缔组织基质的过度产生和沉积为特征的人类真皮区特有的纤维代谢性疾病,主要包括增生性瘢痕和瘢痕疙瘩,其治疗是皮肤外科临床医师常常面临的难题.我们应用计算机检索近10年来Medline相关病理性瘢痕治疗的中外文献计89篇.概述了病理性瘢痕的病理生理研究.重点对不同治疗方法 的疗效、副作用、作用机制进行归纳.治疗方法 有手术治疗、压力治疗、放射治疗、激光治疗、冷冻治疗、糖皮质激素注射治疗、抗肿瘤药治疗、抗组胺药、细胞因子相关治疗及基因治疗.目前尚无特效的治疗方法 ,不同类型的病理性瘢痕需要采用多种治疗方法 综合治疗.     

Extract of Aneilema keisak inhibits transforming growth factor‐β‐dependent signalling by inducing Smad2 downregulation in keloid fibroblasts

Keloids are characterised by the excessive accumulation of extracellular matrix (ECM), especially overabundant collagen formation. In keloid fibroblasts (KFs), transforming growth factor (TGF)‐β‐dependent signalling is closely associated with a variety of keloid pathologic responses such as ECM production and fibroblast overgrowth. Thus, inhibition of TGF‐β signalling would be a potential therapeutic approach to prevent keloid scar formation. Thereby, we aimed to identify a novel TGF‐β signalling blocker among natural products using a simplified screening approach. We discovered that the extract of Aneilema keisak (A.K‐Ex) lowered TGF‐β‐dependent signalling by reducing Smad2 protein levels. Given that KFs showed altered dependency on TGF‐β for survival and proliferation, A.K‐Ex‐mediated reduction in Smad2 protein levels significantly inhibited the major characteristics of KFs such as cell growth, migration and collagen synthesis, suggesting that A.K‐Ex exhibits possible therapeutic activity on keloids.     

Epithelial regulation of mesenchymal tissue behavior

Fibroproliferative scars are an important clinical problem, and yet the mechanisms that regulate scar formation remain poorly understood. This study explored the hypothesis that the epithelium has a critical role in dictating scar formation, and that these interactions differ in skin and mucosa. Paired skin and vaginal mucosal wounds on New Zealand white (NZW) rabbits diverged significantly; the cutaneous epithelium exhibited a greater and prolonged response to injury when compared with the mucosa. Microarray analysis of the injured epithelium was performed, and numerous factors were identified that were more strongly upregulated in skin, including several proinflammatory cytokines and profibrotic growth factors. Analysis of the underlying mesenchymal tissue demonstrated a fibrotic response in the dermis of the skin but not the mucosal lamina propria, in the absence of a connective tissue injury. To determine if the proinflammatory factors produced by the epidermis may have a role in dermal fibrosis, an IL-1 receptor antagonist was administered locally to healing skin wounds. In the NZW rabbit model, blockade of IL-1 signaling was effective in preventing hypertrophic scar formation. These results support the idea that soluble factors produced by the epithelium in response to injury may influence fibroblast behavior and regulate scar formation in vivo.     

The renin-angiotensin system in cutaneous hypertrophic scar and keloid formation

Hypertrophic scar and keloid are two types of fibroproliferative conditions that result from excessive extracellular matrix production. The underlying pathological mechanism is not entirely clear. Activation of the renin-angiotensin system (RAS) is associated with fibrosis in various organs. RAS components including angiotensin II (Ang II), angiotensin AT₁ and AT₂ receptors, and angiotensin-converting enzyme (ACE) are expressed in the skin and act independently from the plasma RAS. AT₁ receptors, which are usually the dominating receptor subtype, promote fibrosis and scar formation, while AT₂ receptors inhibit the aforementioned AT₁ receptor-coupled effects. Elevated angiotensin II (Ang II) levels acting on the AT₁ receptor contribute to skin scar formation through increased expression of inflammatory factors such as interleukin-6 (IL-6), angiogenic factors such as vascular endothelial growth factor (VEGF) and fibrinogenic factors such as transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF), while at the same time suppressing the anti-fibrotic tissue inhibitors of matrix metalloproteinase (TIMPs). First, small clinical trials have provided evidence that inhibition of the ACE/Ang II/ AT₁ receptor axis may be effective in the treatment of hypertrophic scars/keloids. This review provides a detailed overview of the current literature on the RAS in skin, wound healing and scar formation and discusses the translational potential of targeting this hormonal system for treatment and prevention of hypertrophic scars and keloids.     

微晶磨削术联合外用重组人表皮生长因子修复皮肤瘢痕105例疗效观察

目的评价微晶磨削术联合重组人表皮生长因子外用溶液(金因肽)对各类型皮肤浅表性瘢痕的疗效。方法对105例浅表性皮肤瘢痕患者采用美国赛诺秀公司生产的MDY-1A微晶磨面机。借助机内压缩空气的压力,将微晶颗粒高速急骤地喷打在皮肤瘢痕表面,造成瘢痕表皮的蜂窝状损伤,再用微晶磨头在瘢痕表面磨削,术后局部外用重组人表皮生长因子外用溶液和抗生素软膏等。结果接受2~6次治疗后,患者原瘢痕表面均平滑,外观改善,有效率达94.29%。结论微晶磨削术联合重组人表皮生长因子外用溶液是修复皮肤浅表性瘢痕的一种简便而有效的方法。     

Dermatopontin expression is decreased in hypertrophic scar and systemic sclerosis skin fibroblasts and is regulated by transforming growth factor-beta1, interleukin-4, and matrix collagen

Dermatopontin is a recently discovered extracellular matrix protein with proteoglycan and cell-binding properties and is assumed to play important roles in cell-matrix interactions and matrix assembly. In this study we examined the expression of dermatopontin mRNA and protein in skin fibroblast cultures from patients with hypertrophic scar and patients with systemic sclerosis. Dermatopontin mRNA and protein levels were reduced in fibroblast cultures from hypertrophic scar lesional skin compared with fibroblasts from normal skin of the same hypertrophic scar patient. Fibroblast cultures from systemic sclerosis patient involved skin also showed significantly reduced expression of dermatopontin compared with normal skin fibroblasts from healthy individuals. We also investigated the effects of cytokines and matrix collagen on dermatopontin expression in normal cultured fibroblasts. Transforming growth factor-beta1 increased dermatopontin mRNA and protein levels, while interleukin-4 reduced dermatopontin expression. Substrate coated with type I collagen reduced dermatopontin mRNA levels, the reduction being more prominent in three-dimensional collagen matrices. Our results suggest that the decreased expression of dermatopontin is associated with the pathogenesis of fibrosis in hypertrophic scar and systemic sclerosis, and that the effect of the cytokines and matrix collagen on dermatopontin may have important implications for skin fibrosis.     

增生性瘢痕发生和演变过程中成纤维细胞生物学功能变化及其意义

目的 探索增生性瘢痕在发生和演变过程中,成纤维细胞生物学功能变化的规律及其意义.方法 选取人不同时期增生性瘢痕组织和正常皮肤组织,进行HE染色观察.另外,分离和培养不同时期瘢痕和正常皮肤中成纤维细胞,RT-PCR分别检测成纤维细胞在转移生长因子（TGF-β1）、血管内皮细胞生长因子（VEGF）、和Ⅰ、Ⅲ胶原mRNA表达水平的变化.结果 HE染色可见正常皮肤细胞和微血管数目较少,早期瘢痕增多,炎症细胞浸润明显.增生期瘢痕成纤维细胞和微血管增多.随病情进展,微血管呈缩窄倾向.消退期瘢痕成纤维细胞减少,微血管狭窄或闭塞.成熟期瘢痕见微血管、成纤维细胞数目进一步减少,微血管管腔小,大部分开放.RT-PCR检测结果发现,正常皮肤来源的成纤维细胞TGF-β1、VEGF和Ⅰ、Ⅲ胶原mRNA有较低表达,早期瘢痕成纤维细胞TGF-β1、VEGF和Ⅰ、Ⅲ胶原mRNA表达水平开始升高,在增生期表达到达高峰,消退期瘢痕的表达开始下降,到成熟期表达最低.结论 增生性瘢痕发生和演变过程中,成纤维细胞功能存在动态改变,这种动态改变与瘢痕的发生和消退成熟的病理变化相关.