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猪模型中全层切除伤口愈合过程中瘢痕形成相关蛋白质的表达谱

Expression profile of proteins involved in scar formation in the healing process of full-thickness excisional wounds in the porcine model.

作者信息

Ulrich Magda M W, Verkerk Michelle, Reijnen Linda, Vlig Marcel, van den Bogaerdt Antoon J, Middelkoop Esther

机构信息

Association of Dutch Burn Centres, Beverwijk, The Netherlands.

出版信息

Wound Repair Regen. 2007 Jul-Aug;15(4):482-90. doi: 10.1111/j.1524-475X.2007.00255.x.

Abstract

Scar formation in deep dermal wounds is associated with excessive collagen deposition and contraction. Increased collagen synthesis and decreased collagen degradation are the mechanisms through which this form of fibrosis can occur. Another factor might be a different kind of collagen cross-linking seen in fibrotic skin diseases. This type of cross-linking is dependent on the enzyme lysyl hydroxylase-2b. In this study, we examined the expression profile of the potential key players in scar formation in time in healing of acute wounds. Collagen types I and III, lysyl hydroxylase-2b, alpha-smooth muscle actin, transforming growth factor betas, and the matrix metalloproteinases and their inhibitor mRNA levels were determined. All genes examined show distinct expression patterns over time. The expression of lysyl hydroxylase-2b peaks at day 7, and precedes collagen types I and III expression. Eight weeks after wounding, the scars showed an increased level of lysyl hydroxylase-2b-mediated collagen cross-linking. This study shows that the fibrosis-specific type of cross-linking of collagen seen in human hypertrophic scarring also plays a role in this animal model of wound healing. Moreover, the expression of the putative gene responsible for this type of cross-linking, the lysyl hydroxylase-2b, is elevated during wound healing.

摘要

真皮深层伤口的瘢痕形成与胶原蛋白过度沉积和收缩有关。胶原蛋白合成增加和降解减少是这种纤维化形式发生的机制。另一个因素可能是在纤维化皮肤病中看到的一种不同类型的胶原蛋白交联。这种类型的交联依赖于赖氨酰羟化酶-2b。在本研究中,我们及时检测了急性伤口愈合过程中瘢痕形成潜在关键参与者的表达谱。测定了I型和III型胶原蛋白、赖氨酰羟化酶-2b、α-平滑肌肌动蛋白、转化生长因子β以及基质金属蛋白酶及其抑制剂的mRNA水平。所有检测的基因随时间呈现出不同的表达模式。赖氨酰羟化酶-2b的表达在第7天达到峰值,并先于I型和III型胶原蛋白的表达。受伤8周后,瘢痕显示赖氨酰羟化酶-2b介导的胶原蛋白交联水平增加。这项研究表明,在人类增生性瘢痕中看到的纤维化特异性胶原蛋白交联类型在这种伤口愈合动物模型中也起作用。此外,负责这种交联类型的假定基因赖氨酰羟化酶-2b在伤口愈合过程中表达升高。

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