瘢痕疙瘩的遗传及局部微环境病因学研究现状

瘢痕疙瘩的发病机制复杂,目前对其病因学研究主要围绕遗传因素、环境因素、细胞因素和免疫因素.研究表明,瘢痕疙瘩遗传相关的多个致病基因通过表观遗传学机制,如DNA甲基化、组蛋白修饰和非编码RNA的改变等,能够影响瘢痕疙瘩形成.在此,本文回顾现有的临床和实验研究,分析了有关遗传和局部微环境因素病因的研究现状,以期为瘢痕疙瘩的...     

瘢痕疙瘩发病机制及术后放疗研究进展

目前研究表明遗传、伤口张力、感染、内分泌因素等均可导致瘢痕疙瘩的发生和发展。单一治疗瘢痕疙瘩的效果不能令人满意，应多种方法联合治疗，手术切除联合放疗是治疗瘢痕疙瘩较有效的方案之一。本文就近年来瘢痕疙瘩的发病机制及术后放疗作一综述。     

成纤维细胞活化蛋白在瘢痕疙瘩组织中的表达及意义

 目的:了解成纤维细胞活化蛋白（FAP）在瘢痕疙瘩组织中的表达情况，探讨FAP在瘢痕疙瘩发病机制中的作用。方法:采用免疫组化染色技术检测30例瘢痕疙瘩组织（病例组）和20例正常皮肤组织（对照组）中FAP的表达强度，并比较两组间及瘢痕疙瘩不同临床分级之间FAP表达阳性率的差异。结果:病例组瘢痕疙瘩组织中FAP在成纤维细胞和血管内皮细胞内表达，阳性率为73.33％；对照组正常皮肤组织中未见FAP表达，两组间FAP表达阳性率比较,差异有统计学意义（  X²=26.19,P=0.001）；瘢痕疙瘩临床分级中,轻度与重度之间及中度与重度之间比较，FAP表达阳性率差异均有统计学意义（P值分别为0.002、0.006）。结论:瘢痕疙瘩组织中FAP表达阳性率明显高于正常皮肤组织；瘢痕疙瘩临床分级越严重，FAP表达阳性率越高；FAP可能参与瘢痕疙瘩的发病机制，针对FAP的干预可能有助于瘢痕疙瘩的治疗。     

瘢痕疙瘩成纤维细胞研究进展

近10年来瘢痕疙瘩发病机制的研究有了很大的进展，对组织标本及体外培养的成纤维细胞生长、胶原代谢的分析研究，充分说明了瘢痕疙瘩成纤维细胞的异常性，通过对瘢痕疙瘩成纤维细胞的进一步研究，并随着细胞生物学、分子生物学、免疫学等在创面愈合领域的不断深入，有望在不久的将来揭开瘢痕疙瘩形成之谜。     

瘢痕疙瘩的治疗

瘢痕疙瘩发病机制不明,治疗比较困难,临床多采用综合疗法。外科手术切除联合放射治疗,或者联合瘢痕内注射糖皮质激素是治疗瘢痕疙瘩的一线疗法。放疗通常有浅层x线、电子束,其致癌性通常较小。硅凝胶片和压力疗法通常作为基础性辅助治疗,对不同病期的瘢痕疙瘩均有一定疗效,表现为瘢痕变软、变平,主观症状得到改善。抗瘢痕疙瘩药物主要包括积雪草苷和α-积雪草苷乳膏、5％咪喹莫特乳膏等。基因治疗和某些生物制剂可能是瘢痕疙瘩治疗的发展方向。个性化评估瘢痕疙瘩患者的病情,综合运用以上治疗方法可以较好地减轻皮损。     

瘢痕疙瘩的遗传学及相关基因研究最新进展

目前认为瘢痕疙瘩为多基因遗传病,其确切病因不明。近年来流行病学研究表明瘢痕疙瘩发病有一定的家族聚集性,遗传和分子流行病学研究进一步揭示了一些特定基因如P53,Fas,c-myc,c-fos,ras和BCL-2等特定基因多态性在人类瘢痕疙瘩发病过程中的相关性和作用,而另一些基因如转化生长因子TGF-β、胰岛素样生长因子IGF、血小板源性生长因子PDGF、表皮生长因子EGF与瘢痕疙瘩的相关性则需要进一步研究证明,这些研究为瘢痕疙瘩的发病机制提供了遗传学理论依据。     

瘢痕疙瘩发病机制的研究

瘢痕疙瘩是一种以侵袭性生长为特点的良性肿瘤。瘢痕疙瘩有一定的遗传易感性,瘢痕疙瘩患者多有家族倾向性及家族聚集性,属于常染色体显性遗传。皮肤创伤愈合过程中受多种细胞因子,信号传导通路,细胞外基质的影响下,成纤维细胞的过度增殖和细胞外基质中胶原的沉积而导致瘢痕疙瘩的形成。近年来,很多学者通过分子生物学研究得出瘢痕疙瘩形成过程中各种基因作用机制及细胞因子的表达异常,对瘢痕疙瘩的诊断及治疗提供了一个新方向。     

皮损内注射治疗瘢痕疙瘩的研究进展

瘢痕疙瘩是一种以皮肤结缔组织增生和侵袭性生长为主要特征的病理性瘢痕。多在外伤、炎症、手术后形成,好发于胸前、肩胛部、耳垂等部位。暴露部位瘢痕疙瘩影响美观,功能区皮损影响局部活动,且瘢痕疙瘩常伴瘙痒、疼痛、局部过度敏感等,对患者造成沉重心理负担,严重者生活质量受到影响。虽然瘢痕疙瘩在临床上治疗方法多样,但因其形成机制尚不明确,复发率高,故是外科治疗的难题。皮损内注射治疗已广泛应用于国内外瘢痕疙瘩的治疗,本文对其作以综述。     

瘢痕疙瘩的成因及治疗新进展

瘢痕疙瘩有着过度生长、侵犯邻近组织、手术切除后极易复发、治疗效果不佳等特点,成为当今整形外科和皮肤科的一个重大难题。瘢痕疙瘩发病机制迄今未明,本文从遗传机制、生物活性因子、胶原代谢等方面综述了近几年来对瘢痕疙瘩病因研究的最新进展,并对瘢痕疙瘩的治疗方法进行了总结。     

转化生长因子β1在瘢痕疙瘩防治中的研究进展

瘢痕疙瘩的形成是多种基因通过多种途径相互作用的结果。转化生长因子β1(TGF-β1)在瘢痕疙瘩的发病机制中起了重要的促进作用,它可以通过TGF-β1/Smads信号通路、丝裂原活化蛋白激酶等发挥其生物学效应。目前研究表明,对TGF-β1作用途径的干预可以影响纤维化发展,从而防治瘢痕疙瘩形成。现对有关TGF-β1在瘢痕疙瘩中作用机制及其在瘢痕疙瘩防治中的相关研究进展作一综述。     

Experimental Keloid Scar Models: A Review of Methodological Issues

Background: Keloid scars are benign fibrous proliferations in the dermis that arise after dermal trauma. The scars are raised in appearance and extend beyond the boundaries of the original wound. Scarring in predisposed individuals is out of proportion to the severity of the inciting wound. Current treatments sometimes yield early benefit but scars often resume exuberant growth. The pathophysiology of keloid scars is still poorly understood. In order for new treatments to be developed, the mechanisms leading to the formation of keloid scars must be further elucidated. The search for improved experimental models is of critical importance because such models have an important role to play in both the study of keloid formation and in the development of new therapies. Objective: The objective of this article is to introduce the reader to the experimental models available for studying keloid scars and to outline the advantages and limitations of animal and tissue culture models. Conclusion: Both models may help to elucidate the pathways of keloid formation and promote development and testing of therapies. Tissue culture is better suited to studies of pathogenesis, whereas the animal models are more suitable for therapeutic testing.     

Phenotypic profiling of keloid scars using FT-IR microspectroscopy reveals a unique spectral signature

Keloid disease (KD) is a quasineoplastic fibroproliferative tumour of unknown origin causing a progressive, recurrent dermal lesion. KD is not homogeneous in nature and shows phenotypic structural differences between its distinct peripheral margins compared to its centre. The keloid margin is often symptomatically more active with increased dermal cellularity, compared to a symptomatically dormant and hypocellular centre of lesion. The aim of this study was to delineate the morphological components of a keloid scar tissue by measuring the differences between various anatomical locations within the keloid tissue, such as the margin and the centre of the lesion compared to its surrounding normal skin using Fourier transform infrared (FT-IR) microspectroscopy. FT-IR microspectroscopy is a technique that produces spectra with detailed molecular biochemical information inherent of the chemical structure. Chemical maps were constructed on extralesional cross sections taken from six keloid scars. H&E stained sections were used to confirm diagnosis of keloid and orientate the experimental cross sections prior to FT-IR. Spectral band assignment and principal components analysis were conducted. Distinct vibrational bands (100 spectra) were observed using FT-IR spectroscopy. Partial least squares discriminant analysis, with bootstrapping (10,000 analyses), identified whether a spectrum was from the keloid or normal tissue showing an average accuracy of 84.8%, precision of 80.4%, specificity of 76.2%, and sensitivity of 92.9%. FT-IR microspectroscopy showed significant differences in spectral profiles in keloid tissue in different anatomical locations within the cross section. We believe that this proof-of-concept study may help substantiate the use of FTIR spectroscopy in keloid diagnosis and prognosis.     

Genome scans provide evidence for keloid susceptibility loci on chromosomes 2q23 and 7p11

Keloids are proliferative fibrous growths that result from an excessive tissue response to skin trauma. They often occur sporadically, but in some families a genetic predisposition to keloids has been observed. Here we studied two families with an autosomal dominant inheritance pattern of keloids. One African-American family showed a high degree of variability in the extent of keloid formation between family members, whereas the second family from Japan showed a pattern of full penetrance and the formation of only small keloids. We performed a genome-wide linkage search for genes predisposing to keloid formation in these two families. We identified linkage to chromosome 2q23 (maximal two-point LOD score of 3.01) for the Japanese family. The African-American family showed evidence for a keloid susceptibility locus on chromosome 7p11 (maximal two-point LOD score of 3.16). The observed locus heterogeneity in autosomal dominant keloid disease is consistent with the clinical heterogeneity of this scarring disorder. Dense microsatellite analysis in these two loci was performed and candidate genes were identified. This study provides the first genetic evidence for keloid susceptibility loci and serves as a basis for the identification of responsible genes.     

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.     

Collagen gene expression in keloids: analysis of collagen metabolism and type I, III, IV, and V procollagen mRNAs in keloid tissue and keloid fibroblast cultures

Regulation of collagen gene expression was studied in keloids and fibroblast cultures established from keloid biopsies from 9 patients. The collagen concentration in keloid tissue was not different from that in normal skin. The activities of 2 enzymes catalyzing intracellular collagen biosynthesis, prolyl 4-hydroxylase (PH) and galactosylhydroxylysyl glucosyltransferase (GGT) were significantly elevated in the keloids, the mean increase in the former enzyme being 5-fold and in the latter 3-fold with respect to the controls. The mean procollagen production rate in the keloid fibroblasts was at the control level, with only 1 keloid cell line showing a procollagen synthesis rate higher than the mean value + 2 SD of the controls. The mean PH and GGT activities of the keloid fibroblasts were not elevated, but PH activity in 2 cell lines and GGT activity in 1 cell line were higher than the mean + 2 SD for the controls. Cellular type I, III, IV, and V procollagen mRNAs were measured by slot blot hybridization using specific human cDNA clones for the various collagen types. The amounts of type I, III, and V procollagen mRNAs corresponded to the ratios in which these collagen types are produced by fibroblasts. No synthesis of type IV procollagen mRNA by keloid fibroblasts was observed. The total amount of type I and III procollagen mRNAs correlated significantly (p less than 0.01) with the procollagen synthesis rate measured after radioactive labeling of the cells in the keloid and control fibroblasts, indicating that collagen production in these cells is mainly controlled by regulating the final steady state levels of collagen mRNA. The results suggest that fibroblasts isolated from keloids often synthesize normal amounts of collagen.     

Surgical management for large chest keloids with internal mammary artery perforator flap

Therapy for large symptomatic keloids is often plagued with complicated reconstruction manner and recurrence. This article reports a rare treatment combination for a chest keloid with internal mammary artery perforator flap reconstruction and radiation therapy. We excised the keloid and covered the defect with an internal mammary artery perforator flap. Immediate electron-beam irradiation therapy was applied on the second postoperative day. There was no sign of recurrence over the follow-up period of 18 months. The combination of internal mammary artery perforator flap and immediate radiation therapy is useful when faced with chest keloids of similar magnitude and intractability.     

胃泌素释放肽及其受体在瘢痕疙瘩中的表达和临床意义

目的研究瘢痕疙瘩内胃泌素释放肽(GRP)及其受体(GRPR)的表达,探讨其在瘢痕疙瘩中的作用。方法使用蛋白质印迹分析检测瘢痕疙瘩及正常皮肤组织内的GRP含量,实时定量PCR检测瘢痕疙瘩及正常成纤维细胞上的GRPR表达。结果瘢痕疙瘩的GRP及GRPR表达均较正常表达升高,差异有统计学意义(P<0.05)。结论瘢痕疙瘩的GRP及GRPR过表达可能在瘢痕疙瘩的发生发展过程中有重要作用。     

Altered circulating endothelial progenitor cells in patients with keloid

Evidence has suggested that vascular endothelial growth factor (VEGF), a crucial growth factor in regulating endothelial progenitor cells (EPCs), plays a central role in keloid formation. However, the levels of circulating EPCs in patients with keloid have not yet been explored. The aim of this study was to determine the number of circulating EPCs in patients with keloid. Circulating EPCs (defined as CD45? CD34+CD133+VEGFR2+cells) and VEGF levels from 39 patients with keloid and 22 healthy controls (HCs) were assessed by flow cytometry and ELISA, respectively. EPCs were detectable in the peripheral blood of patients with keloid. The number of circulating EPCs and the levels of plasma VEGF were significantly higher in patients with keloid than in HCs. However, no correlation was found between the number of circulating EPCs and the serum VEGF levels. This study provides the first evidence that EPCs are increased in the peripheral blood of patients with keloid. Understanding the roles of EPCs in keloid fromation may lead to the development of novel therapeutic strategies for keloid.