Aging is associated with reduced deposition of specific extracellular matrix components, upregulation of angiogenesis, and an altered inflammatory response in a murine incisional wound healing model

Aging is associated with reduced deposition of specific extracellular matrix components, upregulation of angiogenesis, and an altered inflammatory response in a murine incisional wound healing model
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DOI:
10.1111/1523-1747.ep12289705
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发表时间:
1997-04-01
影响因子:
6.5
通讯作者:
Ferguson, MWJ
Ferguson, MWJ
中科院分区:
医学1区
文献类型:
--
作者:
Ashcroft, GS;Horan, MA;Ferguson, MWJ

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衰老损害伤口愈合的概念在很大程度上是未经证实的,文献是矛盾的,因为糟糕的实验设计和未能充分表征动物模型。本研究在一个具有良好特征的衰老小鼠群体中使用标准化的皮肤切口伤口验证了衰老延缓伤口修复速度的假设。在正常皮肤成分与年龄相关变化的背景下,观察到明显的愈合差异,老年小鼠伤口中纤维连接蛋白免疫染色下降,炎症反应延迟,再上皮化,细胞外基质成分出现,老年动物伤口中硫酸肝素和血管染色均在较晚时间点意外增加。尽管老龄小鼠伤口中的胶原I和III沉积总体减少,但皮肤组织与正常皮肤的篮状胶原结构惊人地相似。相比之下,幼龄动物出现了异常、密集的疤痕。有趣的是,一些与年龄相关的疤痕质量和炎症细胞谱的变化与胎儿伤口愈合的变化相似。幼龄动物的愈合速度似乎是以牺牲疤痕质量为代价的,这可能是由于炎症反应的改变。
The concept that aging impairs wound healing is largely unsubstantiated, the literature being contradictory because of poor experimental design and a failure to adequately characterize animal models, This study tested the hypothesis that aging retards the rate of wound repair using standardized cutaneous incisional wounds in a well-characterized aging mouse colony. Against the background of age-related changes in normal dermal composition, marked differences in healing were observed, Immunostaining for fibronectin was decreased in the wounds of the old mice, with a delay in the inflammatory response, re-epithelialization, and the appearance of extracellular matrix components, Heparan sulfate and blood vessel staining were both unexpectedly increased in the wounds of the old animals at late time points. Despite an overall decrease in collagen I and III deposition in the wounds of old mice, the dermal organization was surprisingly similar to that of normal dermal basket-weave collagen architecture. By contrast, young animals developed abnormal, dense scars. Intriguingly, some of these age-related changes in scar quality and inflammatory cell profile are similar to those seen in fetal wound healing. The rate of healing in young animals appears to be increased at the expense of the scar quality, perhaps resulting from an altered inflammatory response.