Protein-centric omics analysis reveals circulating complements linked to non-viral liver diseases as potential therapeutic targets
Background/Aims To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets. Methods We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases....
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Korean Association for the Study of the Liver
2024-01-01
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| Series: | Clinical and Molecular Hepatology |
| Subjects: | |
| Online Access: | http://e-cmh.org/upload/pdf/cmh-2023-0343.pdf |
| _version_ | 1797360104741273600 |
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| author | Yingzhou Shi Hang Dong Shiwei Sun Xiaoqin Wu Jiansong Fang Jianbo Zhao Junming Han Zongyue Li Huixiao Wu Luna Liu Wanhong Wu Yang Tian Guandou Yuan Xiude Fan Chao Xu |
| author_facet | Yingzhou Shi Hang Dong Shiwei Sun Xiaoqin Wu Jiansong Fang Jianbo Zhao Junming Han Zongyue Li Huixiao Wu Luna Liu Wanhong Wu Yang Tian Guandou Yuan Xiude Fan Chao Xu |
| author_sort | Yingzhou Shi |
| collection | DOAJ |
| description | Background/Aims To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets. Methods 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. Results In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 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 diseaserelated proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network. Conclusions 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. |
| first_indexed | 2024-03-08T15:34:32Z |
| format | Article |
| id | doaj.art-6e944936cb084077bf1489412e344ed6 |
| institution | Directory Open Access Journal |
| issn | 2287-2728 2287-285X |
| language | English |
| last_indexed | 2024-03-08T15:34:32Z |
| publishDate | 2024-01-01 |
| publisher | Korean Association for the Study of the Liver |
| record_format | Article |
| series | Clinical and Molecular Hepatology |
| spelling | doaj.art-6e944936cb084077bf1489412e344ed62024-01-10T01:29:36ZengKorean Association for the Study of the LiverClinical and Molecular Hepatology2287-27282287-285X2024-01-01301809710.3350/cmh.2023.03431871Protein-centric omics analysis reveals circulating complements linked to non-viral liver diseases as potential therapeutic targetsYingzhou Shi0Hang Dong1Shiwei Sun2Xiaoqin Wu3Jiansong Fang4Jianbo Zhao5Junming Han6Zongyue Li7Huixiao Wu8Luna Liu9Wanhong Wu10Yang Tian11Guandou Yuan12Xiude Fan13Chao Xu14 Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China Northern Ohio Alcohol Center, Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, OH, USA Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China Division of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education; Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China Department of Endocrinology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, ChinaBackground/Aims To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets. Methods 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. Results In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 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 diseaserelated proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network. Conclusions 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.http://e-cmh.org/upload/pdf/cmh-2023-0343.pdfliver diseasescomplement system proteinsmendelian randomization analysisdrug repositioning |
| spellingShingle | Yingzhou Shi Hang Dong Shiwei Sun Xiaoqin Wu Jiansong Fang Jianbo Zhao Junming Han Zongyue Li Huixiao Wu Luna Liu Wanhong Wu Yang Tian Guandou Yuan Xiude Fan Chao Xu Protein-centric omics analysis reveals circulating complements linked to non-viral liver diseases as potential therapeutic targets Clinical and Molecular Hepatology liver diseases complement system proteins mendelian randomization analysis drug repositioning |
| title | Protein-centric omics analysis reveals circulating complements linked to non-viral liver diseases as potential therapeutic targets |
| title_full | Protein-centric omics analysis reveals circulating complements linked to non-viral liver diseases as potential therapeutic targets |
| title_fullStr | Protein-centric omics analysis reveals circulating complements linked to non-viral liver diseases as potential therapeutic targets |
| title_full_unstemmed | Protein-centric omics analysis reveals circulating complements linked to non-viral liver diseases as potential therapeutic targets |
| title_short | Protein-centric omics analysis reveals circulating complements linked to non-viral liver diseases as potential therapeutic targets |
| title_sort | protein centric omics analysis reveals circulating complements linked to non viral liver diseases as potential therapeutic targets |
| topic | liver diseases complement system proteins mendelian randomization analysis drug repositioning |
| url | http://e-cmh.org/upload/pdf/cmh-2023-0343.pdf |
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