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Comprehensive analysis of endoplasmic reticulum-related and secretome gene expression profiles in the progression of non-alcoholic fatty liver disease
Endoplasmic reticulum (ER) is the principal organelle for protein synthesis, such as hepatokines and transmembrane proteins, and is critical for maintaining physiological function. Dysfunction of ER is associated with metabolic disorders. However, the role of ER homeostasis as well as hepatokines in...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412753/ https://www.ncbi.nlm.nih.gov/pubmed/36034446 http://dx.doi.org/10.3389/fendo.2022.967016 |
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author | Gao, Rong Wang, Jin He, Xuemin Wang, Tongtong Zhou, Li Ren, Zhitao Yang, Jifeng Xiang, Xiaoxin Wen, Shiyi Yu, Zhuojun Ai, Heying Wang, Yuchan Liang, Hua Li, Shasha Lu, Yan Zhu, Yanhua Shi, Guojun Chen, Yanming |
author_facet | Gao, Rong Wang, Jin He, Xuemin Wang, Tongtong Zhou, Li Ren, Zhitao Yang, Jifeng Xiang, Xiaoxin Wen, Shiyi Yu, Zhuojun Ai, Heying Wang, Yuchan Liang, Hua Li, Shasha Lu, Yan Zhu, Yanhua Shi, Guojun Chen, Yanming |
author_sort | Gao, Rong |
collection | PubMed |
description | Endoplasmic reticulum (ER) is the principal organelle for protein synthesis, such as hepatokines and transmembrane proteins, and is critical for maintaining physiological function. Dysfunction of ER is associated with metabolic disorders. However, the role of ER homeostasis as well as hepatokines in the progression of non-alcoholic fatty liver disease (NAFLD) remains to be elucidated. Here we comprehensively analyzed the RNA-seq profiles of liver biopsies from 206 NAFLD patients and 10 controls from dataset GSE135251. The co-expression modules were constructed based on weighted gene co-expression network analysis and six co-expression modules were identified, of which brown module stood out to be significantly associated with fibrosis stage and NAFLD activity score (NAS). Subsequently, cytoscape with cytoHubba plugin was applied to identify hub genes in the brown module. GO and KEGG enrichment analysis of the top 20 hub genes were performed and showed the involvement of extracellular matrix formation, collagen synthesis and decomposition, etc. Further, the expression of the top 20 hub genes were found to be a consistent increasing trend as the fibrosis stages and NAS increased, which have been validated both in HFD fed and HFHC fed mice. Among these genes, THY1, PTGDS, TMPRSS3, SPON1, COL1A2, RHBDF1, COL3A1, COL5A1, COL1A1 and IGFBP7 performed well in distinguishing fibrosis stage, while COL1A2, COL3A1, THY1, RHBDF1 and COL1A2 exhibited good capacity to discriminate NAS. Besides, RHBDF1, COL3A1, QSOX1, STING1, COL5A1, IGFBP7, COL4A2, COL1A1, FKBP10 and COL1A2 also showed a strong power in the diagnosis of NAFLD. In addition, COL1A1, COL1A2, COL3A1, COL8A2, IGFBP7, PGF, PTGDS, SPON1, THY1 and TIMP1 were identified as secretome genes from the top 20 hub genes. Of them, circulated THY1 and collagen III level were validated to be significantly elevated in the MCD diet-induced mice. Thus, we provided a systemic view on understanding the pathological roles and mechanisms of ER as well as secretome in NAFLD progression. THY1, COL1A1, COL1A2, COL3A1 and RHBDF1 could be served as candidate biomarkers to evaluate the progression of NAFLD. |
format | Online Article Text |
id | pubmed-9412753 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94127532022-08-27 Comprehensive analysis of endoplasmic reticulum-related and secretome gene expression profiles in the progression of non-alcoholic fatty liver disease Gao, Rong Wang, Jin He, Xuemin Wang, Tongtong Zhou, Li Ren, Zhitao Yang, Jifeng Xiang, Xiaoxin Wen, Shiyi Yu, Zhuojun Ai, Heying Wang, Yuchan Liang, Hua Li, Shasha Lu, Yan Zhu, Yanhua Shi, Guojun Chen, Yanming Front Endocrinol (Lausanne) Endocrinology Endoplasmic reticulum (ER) is the principal organelle for protein synthesis, such as hepatokines and transmembrane proteins, and is critical for maintaining physiological function. Dysfunction of ER is associated with metabolic disorders. However, the role of ER homeostasis as well as hepatokines in the progression of non-alcoholic fatty liver disease (NAFLD) remains to be elucidated. Here we comprehensively analyzed the RNA-seq profiles of liver biopsies from 206 NAFLD patients and 10 controls from dataset GSE135251. The co-expression modules were constructed based on weighted gene co-expression network analysis and six co-expression modules were identified, of which brown module stood out to be significantly associated with fibrosis stage and NAFLD activity score (NAS). Subsequently, cytoscape with cytoHubba plugin was applied to identify hub genes in the brown module. GO and KEGG enrichment analysis of the top 20 hub genes were performed and showed the involvement of extracellular matrix formation, collagen synthesis and decomposition, etc. Further, the expression of the top 20 hub genes were found to be a consistent increasing trend as the fibrosis stages and NAS increased, which have been validated both in HFD fed and HFHC fed mice. Among these genes, THY1, PTGDS, TMPRSS3, SPON1, COL1A2, RHBDF1, COL3A1, COL5A1, COL1A1 and IGFBP7 performed well in distinguishing fibrosis stage, while COL1A2, COL3A1, THY1, RHBDF1 and COL1A2 exhibited good capacity to discriminate NAS. Besides, RHBDF1, COL3A1, QSOX1, STING1, COL5A1, IGFBP7, COL4A2, COL1A1, FKBP10 and COL1A2 also showed a strong power in the diagnosis of NAFLD. In addition, COL1A1, COL1A2, COL3A1, COL8A2, IGFBP7, PGF, PTGDS, SPON1, THY1 and TIMP1 were identified as secretome genes from the top 20 hub genes. Of them, circulated THY1 and collagen III level were validated to be significantly elevated in the MCD diet-induced mice. Thus, we provided a systemic view on understanding the pathological roles and mechanisms of ER as well as secretome in NAFLD progression. THY1, COL1A1, COL1A2, COL3A1 and RHBDF1 could be served as candidate biomarkers to evaluate the progression of NAFLD. Frontiers Media S.A. 2022-08-12 /pmc/articles/PMC9412753/ /pubmed/36034446 http://dx.doi.org/10.3389/fendo.2022.967016 Text en Copyright © 2022 Gao, Wang, He, Wang, Zhou, Ren, Yang, Xiang, Wen, Yu, Ai, Wang, Liang, Li, Lu, Zhu, Shi and Chen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Gao, Rong Wang, Jin He, Xuemin Wang, Tongtong Zhou, Li Ren, Zhitao Yang, Jifeng Xiang, Xiaoxin Wen, Shiyi Yu, Zhuojun Ai, Heying Wang, Yuchan Liang, Hua Li, Shasha Lu, Yan Zhu, Yanhua Shi, Guojun Chen, Yanming Comprehensive analysis of endoplasmic reticulum-related and secretome gene expression profiles in the progression of non-alcoholic fatty liver disease |
title | Comprehensive analysis of endoplasmic reticulum-related and secretome gene expression profiles in the progression of non-alcoholic fatty liver disease |
title_full | Comprehensive analysis of endoplasmic reticulum-related and secretome gene expression profiles in the progression of non-alcoholic fatty liver disease |
title_fullStr | Comprehensive analysis of endoplasmic reticulum-related and secretome gene expression profiles in the progression of non-alcoholic fatty liver disease |
title_full_unstemmed | Comprehensive analysis of endoplasmic reticulum-related and secretome gene expression profiles in the progression of non-alcoholic fatty liver disease |
title_short | Comprehensive analysis of endoplasmic reticulum-related and secretome gene expression profiles in the progression of non-alcoholic fatty liver disease |
title_sort | comprehensive analysis of endoplasmic reticulum-related and secretome gene expression profiles in the progression of non-alcoholic fatty liver disease |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9412753/ https://www.ncbi.nlm.nih.gov/pubmed/36034446 http://dx.doi.org/10.3389/fendo.2022.967016 |
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