The effect of photodamage on the female Caucasian facial stratum corneum corneome using mass spectrometry-based proteomics
The effect of photodamage on the female Caucasian facial stratum corneum corneome using mass spectrometry-based proteomics
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DOI：
10.1111/ics.12426
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发表时间：
2017-12-01
影响因子：
2.3
通讯作者：
Rawlings, A. V.
中科院分区：
文献类型：
--
作者：
Voegeli, R.;Monneuse, J. -M.;Rawlings, A. V.
背景光损伤对面部角质层（SC）的影响尚不清楚。目的描述白人SC从光暴露的脸颊和光保护的耳后（PA）部位的胶带剥离的SC蛋白质组，将对皮肤光损伤进行全面分析，从而更好地了解角质细胞信号通路，并确定治疗光老化皮肤的新分子靶点。白人受试者从他们的脸颊和PA部位连续剥离9条胶带。蛋白质被提取，胰蛋白酶消化的肽进行了分析，通过纳米色谱耦合到一个高分辨率质谱仪。数据依赖性的采集允许蛋白质鉴定，通过Paragon算法的蛋白质Pilot software. Results表皮分化蛋白质的水平的变化是明显的，表明差的表皮分化和SC成熟（角蛋白，皮质包膜（CE）蛋白质）上曝光的脸颊。观察到角蛋白脱屑（有利于脱屑）和聚丝蛋白溶解（有利于减少聚丝蛋白加工）的蛋白酶-抗蛋白酶平衡差异。12 R-LOX，一种CE成熟酶，在光损伤的皮肤中减少，但不减少转氨酶。信号角质形成细胞转导途径标志物的变化尤其通过下游信号传导标志物如钙网蛋白（未折叠蛋白反应; UPR）水平的降低和分层蛋白（雷帕霉素靶点; mTOR）水平的增加来证明。关键蛋白酶体亚基（亚基β-6）水平降低明显表明蛋白质稳态受损。最后，关键的抗氧化蛋白的上调，除了过氧化氢酶。ConclusionClear的例子差的角质形成细胞分化和相关的代谢和信号通路，连同减少SC成熟确定在光损伤的面部SC。角膜细胞不成熟是显而易见的CE蛋白的变化。特别地，12 R-LOX的减少是光损伤皮肤中的新发现，并支持SC成熟的缺乏。此外，微丝蛋白溶解减少，而角质固定增强。从我们的研究结果，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，可能导致受损的角质形成细胞蛋白稳态之间的串扰差。叠加在这些畸变上的是明显增强的mTOR通路，其也有助于减少SC形成和成熟。我们的研究结果清楚地表明，光损伤的脸颊SC的角质细胞支架紊乱。
BackgroundThe effect of photodamage on facial stratum corneum (SC) is still poorly understood.ObjectiveTo 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.MethodsFemale 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.ResultsChanges 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.ConclusionClear 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.