Proteomic analysis of scleroderma lesional skin reveals activated wound healing phenotype of epidermal cell layer
Proteomic analysis of scleroderma lesional skin reveals activated wound healing phenotype of epidermal cell layer
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DOI：
10.1093/rheumatology/ken370
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发表时间：
2008-12-01
期刊：
影响因子：
5.5
通讯作者：
Stratton, R.
中科院分区：
文献类型：
--
作者：
Aden, N.;Shiwen, X.;Stratton, R.
客观的。使用蛋白质组学分析来识别 SSc 患者皮肤中丰度发生变化的蛋白质。方法。从 12 名弥漫性 SSc 患者和 12 名健康对照者的前臂受累皮肤中获取 4 毫米切除活检组织。二维凝胶电泳用于分离和定义正常和 SSc 皮肤活检材料中的蛋白质。通过质谱正式鉴定了疾病中丰度改变的蛋白质。通过免疫组织化学证实表皮异常。结果。蛋白质组学分析显示，参与细胞外基质生成、肌成纤维细胞收缩性、能量代谢和氧化应激反应的蛋白质丰度发生了变化。此外，表皮特有的和参与表皮细胞分化的蛋白质在疾病中发生了大量改变。 SSc 表皮增厚，有核细胞层扩张，并表现出基底标记角蛋白 14 的异常持续、成熟标记角蛋白 1/10 的延迟表达以及角蛋白 6 和 16 的诱导，这些角蛋白 6 和 16 通常不存在于毛囊间皮肤中，并在表皮损伤后诱导。这些变化与伤口愈合过程中看到的激活表型非常相似。结论。与先前的 SSc 发病机制模型一致，这些数据显示最近发病的 SSc 患者受累皮肤的收缩性增加、细胞外基质增加以及对氧化应激的反应。此外，我们还发现 SSc 表皮具有激活的伤口愈合表型。这些发现很重要，因为损伤激活的表皮细胞在伤口修复过程中诱导和调节局部成纤维细胞。
Objective. To identify using proteomic analysis, proteins of altered abundance in the skin of patients with SSc.Methods. 4 mm excision biopsies were obtained from the forearm involved skin of 12 diffuse SSc patients and 12 healthy controls. Two-dimensional gel electrophoresis was used to separate and define proteins in normal and SSc skin biopsy material. Proteins of altered abundance in the disease were formally identified by mass spectroscopy. Abnormalities of the epidermis were confirmed by immunohistochemistry.Results. Proteomic analysis revealed altered abundance of proteins involved in extracellular matrix production, myofibroblast contractility, energy metabolism and response to oxidative stress. In addition, proteins specific to the epidermis and involved in epidermal cell differentiation were altered in abundance in the disease. SSc epidermis is thickened, has an expanded nucleated cell layer, and exhibits abnormal persistence of basal marker keratin 14, delayed expression of maturation markers keratin 1/10 and the induction of keratins 6 and 16, normally absent from interfollicular skin and induced following epidermal injury. These changes closely resemble the activated phenotype seen during wound healing.Conclusions. Consistent with previous models of SSc pathogenesis these data are showing increased contractility, increased extracellular matrix and response to oxidative stress in the involved skin of recent onset SSc patients. In addition, we show that SSc epidermis has an activated, wound healing phenotype. These findings are important because epidermal cells activated by injury induce and regulate local fibroblasts during wound repair.