Philadelphia VA Medical Center, Philadelphia, PA, USA.
Photochem Photobiol. 2011 May-Jun;87(3):690-8. doi: 10.1111/j.1751-1097.2011.00911.x. Epub 2011 Mar 9.
Human cutaneous photodamage is a major medical problem that includes premature aging and fragility of the skin. Nonxenografted animal models have not been comparatively evaluated for how well they resemble the changes seen in human skin. Here, we sought to identify a suitable mouse model that recapitulates key anatomic, cellular and molecular responses observed in human skin during acute UV exposure. Adult females from three strains of mice, C57BL/6J, SKH1 and Balb/c were exposed to UVB and then evaluated 3 or 20 h after the last irradiation. Skin from UVB-exposed C57BL/6J mice showed features resembling human photodamage, including epidermal thickening, infiltration of the dermis with inflammatory cells, induction of tumor necrosis factor-α (TNF-α) mRNA, accumulation of glycosaminoglycans, particularly hyaluronan in the epidermis and loss of collagen. Hairless SKH1 mouse skin responded similarly, but without any induction of TNF-α mRNA or chondroitin sulfate. Irradiated Balb/c mice were the least similar to humans. Our results in C57BL/6J mice and to a lesser extent in SKH1 mice, show cutaneous responses to a course of UVB-irradiation that mirror those seen in human skin. Proper choice of model is critical for investigating cellular and molecular mechanisms of photodamage and photoaging.
人类皮肤光损伤是一个主要的医学问题,包括皮肤的过早老化和脆弱。尚未对非异种移植的动物模型进行比较评估,以了解它们与人类皮肤所见变化的相似程度。在这里,我们试图确定一种合适的小鼠模型,该模型可以重现人类皮肤在急性 UV 暴露期间观察到的关键解剖、细胞和分子反应。来自三个品系的成年雌性小鼠(C57BL/6J、SKH1 和 Balb/c)接受 UVB 照射,然后在最后一次照射后 3 或 20 小时进行评估。来自 UVB 照射的 C57BL/6J 小鼠的皮肤显示出类似于人类光损伤的特征,包括表皮增厚、真皮炎症细胞浸润、肿瘤坏死因子-α(TNF-α)mRNA 的诱导、糖胺聚糖(特别是表皮中的透明质酸)的积累以及胶原蛋白的丧失。无毛 SKH1 小鼠皮肤的反应类似,但没有任何 TNF-α mRNA 或硫酸软骨素的诱导。接受照射的 Balb/c 小鼠与人类的相似性最小。我们在 C57BL/6J 小鼠中的结果以及在较小程度上在 SKH1 小鼠中的结果表明,皮肤对一系列 UVB 照射的反应与人类皮肤所见的反应相似。选择合适的模型对于研究光损伤和光老化的细胞和分子机制至关重要。