A urinary proteomic landscape of COVID-19 progression identifies signaling pathways and therapeutic options  

作　　者：Yuntao Liu Lan Song Nairen Zheng Jinwen Shi Hongxing Wu Xing Yang Nianci Xue Xing Chen Yimin Li Changqing Sun Cha Chen Lijuan Tang Xiaotian Ni Yi Wang Yaling Shi Jianwen Guo Guangshun Wang Zhongde Zhang Jun Qin 

机构地区：[1]The Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510120,China [2]State Key Laboratory of Proteomics,Beijing Proteome Research Center,National Center for Protein Sciences(Beijing),Beijing Institute of Lifeomics,Beijing 102206,China [3]Beijing Pineal Health Management Co.Ltd,Beijing 102206,China [4]Guangzhou Eighth People’s Hospital,Guangzhou Medical University,Guangzhou 510060,China [5]The First Affiliated Hospital of Guangzhou Medical University,Guangzhou 510120,China [6]Guangzhou Institute of Respiratory Disease,Guangzhou 510120,China [7]Guangdong Provincial Key Laboratory of Research on Emergency in TCM,Guangzhou 510120,China [8]Joint Center for Translational Medicine,Tianjin Medical University Baodi Clinical College,Tianjin 301800,China

出　　处：《Science China(Life Sciences)》2022年第9期1866-1880,共15页中国科学（生命科学英文版）

基　　金：This work was supported by the National Key Research and Development Program of China(2017YFA0505102,2017YFA0505103,2017YFA0505104,2017YFC0908404,2018YFA0507503,2020YFA0708001);the National Natural Science Foundation of China(81874237,31870828);Major National Science and technology projects(2017ZX10305501-006);National Administration of Traditional Chinese Medicine:2019 Project of Building Evidence Based Practice Capacity for TCM(2019XZZX-LG003);Guangdong Key-Area Research and Development Program(2019B020229002,2020B1111300005);Guangzhou Science and Technology Program(201902020009);Guangdong Provincial Key Laboratory of Research on Emergency in TCM(2017B030314176).

摘　　要：Signaling pathway alterations in COVID-19 of living humans as well as therapeutic targets of the host proteins are not clear.We analyzed 317 urine proteomes,including 86 COVID-19,55 pneumonia and 176 healthy controls,and identified specific RNA virus detector protein DDX58/RIG-I only in COVID-19 samples.Comparison of the COVID-19 urinary proteomes with controls revealed major pathway alterations in immunity,metabolism and protein localization.Biomarkers that may stratify severe symptoms from moderate ones suggested that macrophage induced inflammation and thrombolysis may play a critical role in worsening the disease.Hyper activation of the TCA cycle is evident and a macrophage enriched enzyme CLYBL is up regulated in COVID-19 patients.As CLYBL converts the immune modulatory TCA cycle metabolite itaconate through the citramalyl-CoA intermediate to acetyl-CoA,an increase in CLYBL may lead to the depletion of itaconate,limiting its anti-inflammatory function.These observations suggest that supplementation of itaconate and inhibition of CLYBL are possible therapeutic options for treating COVID-19,opening an avenue of modulating host defense as a means of combating SARS-CoV-2 viruses.

关 键 词：COVID-19 URINE PROTEOME CLYBL itaconate 

分 类 号：R563.1[医药卫生—呼吸系统]