Grenier Alexe, Morissette Mathieu C, Rochette Patrick J, Pouliot Roxane
Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec-Université Laval, Quebec City, QC, G1J 1Z4, Canada.
Faculté de Pharmacie, Université Laval, Quebec City, QC, G1V 0A6, Canada.
Sci Rep. 2023 Oct 20;13(1):17969. doi: 10.1038/s41598-023-44868-z.
Skin aging is a multifactorial process influenced by internal and external factors. The contribution of different environmental factors has been well established individually in the last few years. On the one hand, man is rarely exposed to a single factor, and on the other hand, there is very little knowledge about how these extrinsic factors may interact with each other or even how the skin may react to chronic exposure. This study aimed to evaluate the effect on skin aging of a chronic co-exposure of tissue-engineered skin substitutes to cigarette smoke extract (CSE) and solar simulator light (SSL). Skin substitutes were reconstructed according to the self-assembly method and then exposed to CSE followed by irradiation with SSL simultaneously transmitting UVA1, visible light and infrared. When skin substitutes were chronically exposed to CSE and SSL, a significant decrease in procollagen I synthesis and the inhibition of Smad2 phosphorylation of the TGF-β signaling pathway were observed. A 6.7-fold increase in MMP-1 activity was also observed when CSE was combined with SSL, resulting in a decrease in collagen III and collagen IV protein expression. The secretory profile resulting from the toxic synergy was investigated and several alterations were observed, notably an increase in the quantities of pro-inflammatory cytokines. The results also revealed the activation of the ERK1/2 (3.4-fold) and JNK (3.3-fold) pathways. Taken together, the results showed that a synergy between the two environmental factors could provoke premature skin aging.
皮肤老化是一个受内部和外部因素影响的多因素过程。在过去几年中，不同环境因素的作用已分别得到充分证实。一方面，人类很少暴露于单一因素；另一方面，对于这些外在因素如何相互作用，甚至皮肤对长期暴露会如何反应，人们了解甚少。本研究旨在评估组织工程皮肤替代物长期共同暴露于香烟烟雾提取物（CSE）和太阳模拟器光（SSL）对皮肤老化的影响。皮肤替代物根据自组装方法构建，然后暴露于CSE，接着同时用发射UVA1、可见光和红外线的SSL进行照射。当皮肤替代物长期暴露于CSE和SSL时，观察到I型前胶原合成显著减少以及TGF-β信号通路的Smad2磷酸化受到抑制。当CSE与SSL联合使用时，还观察到MMP-1活性增加了6.7倍，导致III型和IV型胶原蛋白表达减少。对由毒性协同作用产生的分泌谱进行了研究，并观察到了一些变化，特别是促炎细胞因子数量增加。结果还显示ERK1/2（3.4倍）和JNK（3.3倍）通路被激活。综上所述，结果表明这两种环境因素之间的协同作用可引发皮肤过早老化。
