Insight into molecular mechanisms underlying hepatic dysfunction in severe COVID-19 patients using systems biology  

作　　者：Sarah Musa Hammoudeh Arabella Musa Hammoudeh Poorna Manasa Bhamidimarri Bassam Mahboub Rabih Halwani Qutayba Hamid Mohamed Rahmani Rifat Hamoudi 

机构地区：[1]Sharjah Institute for Medical Research,College of Medicine,University of Sharjah,Sharjah 27272,United Arab Emirates [2]College of Medicine,University of Sharjah,Sharjah 27272,United Arab Emirates [3]General Surgery Department,Tawam Hospital,SEHA,Al-Ain 15258,United Arab Emirates [4]Rashid Hospital,315 Umm Hurair Second,Dubai Health Authority,Dubai 4545,United Arab Emirates [5]Meakins-Christie Laboratories,McGill University,Quebec H4A 3J1,Montreal,Canada [6]Division of Surgery and Interventional Science,University College London,London W1W 7TY,United Kingdom

出　　处：《World Journal of Gastroenterology》2021年第21期2850-2870,共21页世界胃肠病学杂志（英文版）

基　　金：The University of Sharjah,No.CoV19-0308,No.CoV19-0307 and No:1901090254;Sharjah Research Academy,No:MED001;Al-Jalila Foundation Seed Grant,No.AJF202019.

摘　　要：BACKGROUND The coronavirus disease 2019(COVID-19),a pandemic contributing to more than 105 million cases and more than 2.3 million deaths worldwide,was described to be frequently accompanied by extrapulmonary manifestations,including liver dysfunction.Liver dysfunction and elevated liver enzymes were observed in about 53%of COVID-19 patients.AIM To gain insight into transcriptional abnormalities in liver tissue of severe COVID-19 patients that may result in liver dysfunction.METHODS The transcriptome of liver autopsy samples from severe COVID-19 patients against those of non-COVID donors was analyzed.Differentially expressed genes were identified from normalized RNA-seq data and analyzed for the enrichment of functional clusters and pathways.The differentially expressed genes were then compared against the genetic signatures of liver diseases including cirrhosis,fibrosis,non-alcoholic fatty liver disease(NAFLD),and hepatitis A/B/C.Gene expression of some differentially expressed genes was assessed in the blood samples of severe COVID-19 patients with liver dysfunction using qRT-PCR.RESULTS Analysis of the differential transcriptome of the liver tissue of severe COVID-19 patients revealed a significant upregulation of transcripts implicated in tissue remodeling including G-coupled protein receptors family genes,DNAJB1,IGF2,EGFR,and HDGF.Concordantly,the differential transcriptome of severe COVID-19 liver tissues substantially overlapped with the disease signature of liver diseases characterized with pathological tissue remodeling(liver cirrhosis,Fibrosis,NAFLD,and hepatitis A/B/C).Moreover,we observed a significant suppression of transcripts implicated in metabolic pathways as well as mitochondrial function,including cytochrome P450 family members,ACAD11,CIDEB,GNMT,and GPAM.Consequently,drug and xenobiotics metabolism pathways are significantly suppressed suggesting a decrease in liver detoxification capacity.In correspondence with the RNA-seq data analysis,we observed a significant upregulation of DNAJB1 and HSP9

关 键 词：COVID-19 Hepatic dysfunction Tissue remodeling Metabolic pathways Drug metabolism Hepatic detoxification 

分 类 号：R563.1[医药卫生—呼吸系统] R575[医药卫生—内科学]