Voegeli R, Monneuse J-M, Schoop R, Summers B, Rawlings A V
DSM Nutritional Products Ltd., Wurmisweg 571, 4303, Kaiseraugst, Switzerland.
Phylogene S.A., 62, Route Nationale 113, 30620, Bernis, France.
Int J Cosmet Sci. 2017 Dec;39(6):637-652. doi: 10.1111/ics.12426. Epub 2017 Oct 26.
The effect of photodamage on facial stratum corneum (SC) is still poorly understood.
To describe the SC proteome from tape strippings of Caucasian SC from photoexposed cheek and photoprotected post-auricular (PA) site, a global analysis of photodamage on the skin will be developed leading to a better understanding of keratinocyte signalling pathways and identification of new molecular targets for the treatment of photoaged skin.
Female Caucasian subjects had nine consecutive tape strippings taken from their cheeks and PA site. Proteins were extracted and the trypsin-digested peptides were analysed by nanochromatography coupled to a high-resolution mass spectrometer. Data-dependent acquisition allowed protein identification that was processed by Paragon algorithm of Protein Pilot software.
Changes in the levels of epidermal differentiation proteins were apparent indicating poor epidermal differentiation and SC maturation (keratins, cornified envelope (CE) proteins) on photoexposed cheeks. Differences in protease-anti-protease balance were observed for corneodesmolysis (favouring desquamation) and filaggrinolysis (favouring reduced filaggrin processing). 12R-LOX, a CE maturation enzyme, was reduced in photodamaged skin but not transglutaminases. Changes in signal keratinocyte transduction pathway markers were demonstrated especially by reduced levels of downstream signalling markers such as calreticulin (unfolded protein response; UPR) and increased level of stratifin (target of rapamycin; mTOR). Evidence for impaired proteostasis was apparent by reduced levels of a key proteasomal subunit (subunit beta type-6). Finally, key antioxidant proteins were upregulated except catalase.
Clear examples of poor keratinocyte differentiation and associated metabolic and signalling pathways together with reduced SC maturation were identified in photodamaged facial SC. Corneocyte immaturity was evident with changes in CE proteins. Particularly, the reduction in 12R-LOX is a novel finding in photodamaged skin and supports the lack of SC maturation. Moreover, filaggrinolysis was reduced, whereas corneodesmolysis was enhanced. From our results, we propose that there is a poor cross-talk between the keratinocyte endoplasmic reticulum UPR, proteasome network and autophagy machinery that possibly leads to impaired keratinocyte proteostasis. Superimposed on these aberrations is an apparently enhanced mTOR pathway that also contributes to reduced SC formation and maturation. Our results clearly indicate a corneocyte scaffold disorder in photodamaged cheek SC.
光损伤对面部角质层（SC）的影响仍了解不足。
通过对暴露于光的脸颊和光保护的耳后（PA）部位的白种人SC胶带剥离样本进行蛋白质组学分析，全面了解皮肤光损伤情况，从而更好地理解角质形成细胞信号通路，并确定治疗光老化皮肤的新分子靶点。
白种女性受试者连续9次从脸颊和PA部位进行胶带剥离。提取蛋白质，胰蛋白酶消化后的肽段通过纳色谱与高分辨率质谱仪联用进行分析。数据依赖采集实现蛋白质鉴定，由Protein Pilot软件的Paragon算法处理。
暴露于光的脸颊上，表皮分化蛋白水平变化明显，表明表皮分化和SC成熟不良（角蛋白、角质包膜（CE）蛋白）。在角质层分离（有利于脱屑）和丝聚合蛋白分解（有利于减少丝聚合蛋白加工）方面观察到蛋白酶 - 抗蛋白酶平衡的差异。CE成熟酶12R - LOX在光损伤皮肤中减少，但转谷氨酰胺酶未减少。信号角质形成细胞转导通路标志物发生变化，特别是下游信号标志物如钙网蛋白（未折叠蛋白反应；UPR）水平降低，而分层蛋白（雷帕霉素靶点；mTOR）水平升高。关键蛋白酶体亚基（β6型亚基）水平降低表明蛋白稳态受损。最后，除过氧化氢酶外，关键抗氧化蛋白上调。
在光损伤的面部SC中发现了角质形成细胞分化不良以及相关代谢和信号通路以及SC成熟度降低的明确例子。角质形成细胞不成熟在CE蛋白变化中明显可见。特别是，12R - LOX的减少是光损伤皮肤中的一个新发现，支持SC成熟度不足。此外，丝聚合蛋白分解减少，而角质层分离增强。根据我们的结果，我们提出角质形成细胞内质网UPR、蛋白酶体网络和自噬机制之间存在不良相互作用，这可能导致角质形成细胞蛋白稳态受损。叠加在这些异常之上的是明显增强的mTOR通路，这也导致SC形成和成熟减少。我们的结果清楚地表明光损伤脸颊SC中的角质形成细胞支架紊乱。
