机构：[1]Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China[2]Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education[3]Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China[4]Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China[5]Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China[6]“Chuangxin China” Innovation Base of Stem Cell and Gene Therapy for Endocrine Metabolic diseases, Jinan, Shandong, China[7]Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China[8]Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China[9]Northern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA[10]Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China[11]Clinical Medical College, Ningxia Medical University, Yinchuan, Ningxia, China[12]Division of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets.We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options.In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio [OR] 1.125, 95% confidence interval [CI] 1.018-1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk of primary sclerosing cholangitis (PSC;1.193,1.048-1.357). On the other hand, CFHR1 (0.621, 0.497- 0.776) and CFHR2 (0.824, 0.703-0.965) were inversely associated with the risk of alcohol-related cirrhosis. There were also significant inverse associations between C8 gamma chain (C8G) and PSC (0.832, 0.707-0.979), as well as the risk of metabolic dysfunction-associated steatotic liver disease (1.167, 1.036-1.314). Additionally, C1S (0.111, 0.018-0.672), C7 (1.631, 1.190-2.236), and CFHR2 (1.279, 1.059-1.546) were significantly associated with the risk of hepatocellular carcinoma. Proteins from the complement regulatory networks and various liver disease-related proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network.Our study suggests that certain complement components, including C1S, C1QC, CFHR1, CFHR2, CFHR5, C7, and C8G, might play a role in non-viral liver diseases and could be potential targets for drug development.
基金：
This work was supported by the National Natural Science
Foundation (Grants No. 82200659), and the Natural Science
Foundation of Shandong Province (Grant No. ZR20220H002).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|2 区医学
小类|2 区胃肠肝病学
最新[2025]版：
大类|1 区医学
小类|1 区胃肠肝病学
第一作者：
第一作者机构：[1]Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China[2]Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education[3]Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China[4]Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China[5]Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China[6]“Chuangxin China” Innovation Base of Stem Cell and Gene Therapy for Endocrine Metabolic diseases, Jinan, Shandong, China[7]Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China[8]Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China
通讯作者：
通讯机构：[1]Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China[2]Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education[3]Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China[4]Shandong Clinical Research Center of Diabetes and Metabolic Diseases, Jinan, Shandong, China[5]Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China[6]“Chuangxin China” Innovation Base of Stem Cell and Gene Therapy for Endocrine Metabolic diseases, Jinan, Shandong, China[7]Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Jinan, Shandong, China[8]Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Jinan, Shandong, China[12]Division of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China[*1]Shandong Provincial Hospital, Shandong University, Jinan, Shandong, 250021,China[*2]Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021,China[*3]Division of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China
推荐引用方式(GB/T 7714)：
Shi Yingzhou,Dong Hang,Sun Shiwei,et al.Protein-Centric Omics Analysis Reveals Circulating Complements Linked to Non-Viral Liver Diseases as Potential Therapeutic Targets[J].Clinical And Molecular Hepatology.2023,doi:10.3350/cmh.2023.0343.
APA：
Shi Yingzhou,Dong Hang,Sun Shiwei,Wu Xiaoqin,Fang Jiansong...&Xu Chao.(2023).Protein-Centric Omics Analysis Reveals Circulating Complements Linked to Non-Viral Liver Diseases as Potential Therapeutic Targets.Clinical And Molecular Hepatology,,
MLA：
Shi Yingzhou,et al."Protein-Centric Omics Analysis Reveals Circulating Complements Linked to Non-Viral Liver Diseases as Potential Therapeutic Targets".Clinical And Molecular Hepatology .(2023)
医学