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体外机械压迫对增生性瘢痕中Epilysin(基质金属蛋白酶-28)表达的影响。

Effect of in vitro mechanical compression on Epilysin (matrix metalloproteinase-28) expression in hypertrophic scars.

作者信息

Renò Filippo, Sabbatini Maurizio, Stella Maurizio, Magliacani Gilberto, Cannas Mario

机构信息

Human Anatomy Laboratory, Medical Sciences Department, University of Eastern Piedmont A. Avogadro, Novara, Italy.

出版信息

Wound Repair Regen. 2005 May-Jun;13(3):255-61. doi: 10.1111/j.1067-1927.2005.130307.x.

Abstract

Epilysin, designated matrix metalloproteinase (MMP)-28, is the newest member of this family of proteases expressed by keratinocytes in response to an injury. MMP-28's physiological role and specific substrates are unknown, but its expression pattern suggests that it may serve a role in both tissue homeostasis and wound healing. The aim of this preliminary study was to observe the presence of MMP-28 protein in normotrophic and hypertrophic scars and to evaluate the effect of in vitro mechanical compression on its expression. Biopsies from normotrophic and hypertrophic scars resulting from burns were divided into two samples, one to be used as control (uncompressed) and the other to be compressed in an oxygenated organ chamber for 24 hours in the presence of a serum-free medium, using an electromechanical load transducer (stable pressure = 35 mmHg). Analysis of MMP-28 protein secretion, assessed by Western blot and beta-casein zymography in scar conditioned media, revealed that normotrophic scar did not release MMP-28 in any condition while hypertrophic scar released active MMP-28 both in control conditions and after compression. MMP-28 immunohistochemistry revealed a light protein presence in normotrophic scar keratinocytes and a strong MMP-28 positivity in hypertrophic scar keratinocytes in control conditions, while compression increased MMP-28 staining in normotrophic scar and induced a significant reduction of the protein presence in hypertrophic scar keratinocytes. As it has been suggested that MMP-28 may restructure the skin basal membrane (Saarialho-Kere et al., 2002), our data indicate that mechanical compression directly acts to modulate the remodeling phase of wound healing, altering release and activity of MMP-28 in hypertrophic scars.

摘要

表皮溶解素,即基质金属蛋白酶(MMP)-28,是角质形成细胞在受到损伤时表达的该蛋白酶家族的最新成员。MMP-28的生理作用和特定底物尚不清楚,但其表达模式表明它可能在组织稳态和伤口愈合中发挥作用。本初步研究的目的是观察MMP-28蛋白在正常营养性瘢痕和肥厚性瘢痕中的存在情况,并评估体外机械压迫对其表达的影响。将烧伤后形成的正常营养性瘢痕和肥厚性瘢痕的活检组织分为两个样本,一个用作对照(未受压),另一个在无血清培养基存在的情况下,使用机电负载传感器(稳定压力=35 mmHg)在含氧器官腔中受压24小时。通过对瘢痕条件培养基进行蛋白质印迹和β-酪蛋白酶谱分析来评估MMP-28蛋白分泌,结果显示正常营养性瘢痕在任何条件下均不释放MMP-28,而肥厚性瘢痕在对照条件下和受压后均释放活性MMP-28。MMP-28免疫组织化学显示,在对照条件下,正常营养性瘢痕角质形成细胞中蛋白含量较低,肥厚性瘢痕角质形成细胞中MMP-28呈强阳性,而压迫增加了正常营养性瘢痕中的MMP-28染色,并导致肥厚性瘢痕角质形成细胞中蛋白含量显著降低。由于有人提出MMP-28可能会重塑皮肤基底膜(萨阿里亚霍-凯雷等人,2002年),我们的数据表明,机械压迫直接作用于调节伤口愈合的重塑阶段,改变肥厚性瘢痕中MMP-28的释放和活性。

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