Beatrice Dyring-Andersen1,2,3,4, Marianne Bengtson Løvendorf5, Fabian Coscia1 , Alberto Santos1 , Line Bruun Pilgaard Møller1 , Ana R. Colaço1 , Lili Niu1 , Michael Bzorek6, Sophia Doll7, Jørgen Lock Andersen8, Rachael A. Clark2, Lone Skov 4, Marcel B. M. Teunissen 9 & Matthias Mann 1,7✉

Human skin provides both physical integrity and immunological protection from the external environment using functionally distinct layers, cell types and extracellular matrix. Despite its central role in human health and disease, the constituent proteins of skin have not been systematically characterized. Here, we combine advanced tissue dissection methods, flow cytometry and state-of-the-art proteomics to describe a spatially-resolved quantitative pro-teomic atlas of human skin. We quantify 10,701 proteins as a function of their spatial location and cellular origin. The resulting protein atlas and our initial data analyses demonstrate the value of proteomics for understanding cell-type diversity within the skin. We describe the quantitative distribution of structural proteins, known and previously undescribed proteins specific to cellular subsets and those with specialized immunological functions such as cytokines and chemokines. We anticipate that this proteomic atlas of human skin will become an essential community resource for basic and translational research (https://skin.science/).

1Novo Nordisk Foundation (NNF) Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 2Department of Dermatology, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA. 3 Leo Foundation Skin Immunology Research Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 4Department of Dermatology and Allergology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark. 5 Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark. 6Department of Surgical Pathology, Zealand University Hospital, Næstved, Denmark. 7Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany. 8Department of Plastic and Breast Surgery, Zealand University Hospital, Roskilde, Denmark. 9Department of Dermatology, Amsterdam University Medical Centers, location AMC, Amsterdam, Netherlands. ✉email: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

Jing Ma1,2, Mengting Liu1,2, Yaochi Wang1,2, Cong Xin1,2, Hui Zhang1,2, Shirui Chen1,2, Xiaodong Zheng1,2, Xuejun Zhang1,2, Fengli Xiao1,2,3 , Sen Yang1,2

1Department of Dermatology of First Affiliated Hospital, and Institute of Dermatology, Anhui Medical University, Hefei, Anhui, China

2 Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei, Anhui, China

3 The Center for Scientific Research of Anhui Medical University, Hefei, Anhui, China

Correspondence to: Sen Yang, Fengli Xiao;

email: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。, 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

Keywords: aging, epidermal proteins, skin rejuvenation and aging, proteome, mass spectrometer

Received: February 25, 2020

Accepted: May 27, 2020

Published:

Copyright: Ma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Skin aging is a specific manifestation of the physiological aging process that occurs in virtually all organisms In this study, we used data independent acquisition mass spectrometry to perform a comparative analysis of protein expression in volar forearm skin samples from of 20 healthy young and elderly Chinese individuals. Our quantitative proteomic analysis identified a total of 95 differentially expressed proteins (DEPs) in aged skin compared to young skin. Enrichment analyses of these DEPs (57 upregulated and 38 downregulated proteins) based on the GO, KEGG, and KOG databases revealed functional clusters associated with immunity and inflammation, oxidative stress, biosynthesis and metabolism, proteases, cell proliferation, cell differentiation, and apoptosis. We also found that GAPDH, which was downregulated in aged skin samples, was the top hub gene in a protein-protein interaction network analysis. Some of the DEPs identified herein had been previously correlated with aging of the skin and other organs, while others may represent novel age-related entities. Our non-invasive proteomics analysis of human epidermal proteins may guide future research on skin aging to help develop treatments for age-related skin conditions and rejuvenation.

Yangxin Li1 , Hui Huang 2, Bin Liu3 , Yu Zhang1 , Xiangbin Pan4 , Xi-Yong Yu5 , Zhenya Shen1 and Yao-Hua Song6

Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals. Inflammasome multiprotein complexes are composed of three parts: a sensor protein, an adaptor, and pro-caspase-1. Activation of the inflammasome leads to the activation of caspase-1, which cleaves pro-inflammatory cytokines such as IL-1β and IL-18, leading to pyroptosis. Effectors of the inflammasome not only provide protection against infectious pathogens, but also mediate control over sterile insults. Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases, cancer, and neurodegenerative disorders. Here, we review the role of the inflammasome as a double-edged sword in various diseases, and the outcomes can be either good or bad depending on the disease, as well as the genetic background. We highlight inflammasome memory and the two-shot activation process. We also propose the M- and N-type inflammation model, and discuss how the inflammasome pathway may be targeted for the development of novel therapy. Signal Transduction and Targeted Therapy (2021) 6:247 ; https://doi.org/10.1038/s41392-021-00650-z

1Institute for Cardiovascular Science and Department of Cardiovascular Surgery, First Affiliated Hospital and Medical College of Soochow University, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, Jiangsu, P. R. China; 2 Cardiovascular Department, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, P. R. China; 3 Department of Cardiology, The Second Hospital of Jilin University, Changchun, Jilin, P. R. China; 4 Department of Cardiac Surgery, Fuwai Hospital, Beijing, P. R. China; 5 Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong, P. R. China and 6 Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, Soochow University, National Clinical Research Center for Hematologic Diseases, the First Affiliated Hospital of Soochow University, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China Correspondence: Yangxin Li (该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。) or Zhenya Shen (该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。) or Yao-Hua Song (该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。) These authors contributed equally: Yangxin Li, Hui Huang, Bin Liu.

名誉主任委员：汤钊猷 郑树森 王学浩 陈孝平 董家鸿 窦科峰 滕皋军 夏 强 蔡秀军

主任委员： 樊 嘉

执行主任委员：周俭

副主任委员： 秦叔逵 沈锋 蔡建强 李强 王伟林 陈敏山 孙惠川 向华 吴泓

介入及局部治疗学组组长： 滕皋军

副组长：韩国宏 颜志平 王茂强 刘瑞宝 郭金和 曾昭冲 梁萍 王忠敏

内科及系统治疗组组长：秦叔逵

副组长：任正刚 侯金林 张艳桥 刘秀峰 潘宏铭 毕锋

外科学组组长：周俭

副组长：周伟平 刘连新 文天夫 匡铭 张必翔 陶开山

影像学组组长：曾蒙苏

副组长：梁长虹 陈敏 严福华 徐辉雄 谢晓燕 居胜红

病理学组组长：丛文铭

副组长：纪元 云径平 李增山

委员（按姓氏拼音排序）：

白雪莉 蔡定芳 陈卫霞 陈亚进 陈拥军 成文武 程树群 代 智 戴朝六 董 辉 杜世锁 高 强 郭荣平 郭文治 郭 玮 郭亚兵 花宝金 黄晓武 蒋涵羽 荚卫东 李家平 李 秋 李 涛 李相成 李 汛 李亚明 李晔雄 梁 军 梁 霄 凌昌全 刘 辉 刘 嵘 刘天舒 卢实春 吕国悦 麻 勇 毛一雷 孟志强 彭 涛 任伟新 饶圣祥 施国明 石洪成 石 明 史颖弘 宋天强 谭 广 王建华 王 葵 王 鲁 王 鹏 王文涛 王晓颖 王 征 王志明 向邦德 夏 君 肖永胜 邢宝才 徐建明 徐 钧 杨建勇 杨欣荣 杨业发 杨云柯 姚小红 尹震宇 袁振刚 曾红梅 曾永毅 曾 勇 张博恒 张雷达 张水军 张 倜 张志伟 赵 明 赵永福 郑红刚 周乐杜 朱继业 朱康顺

秘书长： 孙惠川

副秘书长：王 征 史颖弘 刘 嵘 张 岚

秘书组: 肖永胜 杨 春 吴志峰 丁振斌 朱小东 周正君 黄晓勇 韩 红 朱海东 仲斌演 张 巍