Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Medical Proteomics Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Sci Rep. 2018 Jan 11;8(1):521. doi: 10.1038/s41598-017-18282-1.
Alopecia areata (AA) is one of the common hair disorders for which treatment is frequently ineffective and associated with relapsing episodes. Better understanding of disease mechanisms and novel therapeutic targets are thus required. From 10 AA patients, quantitative proteomics using LTQ-Orbitrap-XL mass spectrometer revealed 104 down-regulated, 4 absent, 3 up-regulated and 11 newly present proteins in lesional vs. non-lesional biopsies. Among these, the decreased levels of α-tubulin, vimentin, heat shock protein 70 (HSP70), HSP90, annexin A2 and α-enolase were successfully confirmed by Western blotting. Protein-protein interactions network analysis using STRING tool revealed that the most frequent biological processes/networks of the down-regulated proteins included tissue development, cell differentiation, response to wounding and catabolic process, whereas those for the up-regulated proteins included biological process, metabolic process, cellular transport, cellular component organization and response to stimulus. Interestingly, only 5 increased/newly present proteins were associated with the regulation of immune system, which may not be the predominant pathway in AA pathogenic mechanisms as previously assumed. In summary, we report herein the first proteome dataset of AA demonstrating a number of novel pathways, which can be linked to the disease mechanisms and may lead to discovery of new therapeutic targets for AA.
斑秃（AA）是一种常见的毛发疾病，其治疗方法常常无效，并伴有反复发作。因此，需要更好地了解疾病机制和新的治疗靶点。使用 LTQ-Orbitrap-XL 质谱仪对 10 例 AA 患者进行定量蛋白质组学研究，发现病变与非病变活检组织相比有 104 个下调蛋白、4 个缺失蛋白、3 个上调蛋白和 11 个新出现蛋白。其中，α-微管蛋白、波形蛋白、热休克蛋白 70（HSP70）、HSP90、膜联蛋白 A2 和α-烯醇酶的水平降低通过 Western blot 成功得到了验证。使用 STRING 工具进行蛋白质-蛋白质相互作用网络分析表明，下调蛋白最常见的生物学过程/网络包括组织发育、细胞分化、对创伤的反应和分解代谢过程，而上调蛋白的生物学过程、代谢过程、细胞运输、细胞成分组织和对刺激的反应。有趣的是，只有 5 个上调/新出现的蛋白与免疫系统的调节有关，这可能不像以前假设的那样，是 AA 发病机制中的主要途径。总之，我们在此报告了第一个 AA 的蛋白质组数据集，该数据集显示了许多新的途径，这些途径可能与疾病机制有关，并可能为 AA 发现新的治疗靶点。
