Comprehensive analysis of endoplasmic reticulum-related and secretome gene expression profiles in the progression of non-alcoholic fatty liver disease

作者：Rong Gao, Jin Wang, Xuemin He, Tongtong Wang, Li Zhou, Zhitao Ren, Jifeng Yang, Xiaoxin Xiang, Shiyi Wen, Zhuojun Yu, Heying Ai, Yuchan Wang, Hua Liang, Shasha Li, Yan Lü, Yanhua Zhu, Guojun Shi, Yanming Chen · 发表于：Frontiers in Endocrinology · 年份：2022 · DOI：10.3389/fendo.2022.967016 · 被引用次数：25 · 研究领域：Liver Disease Diagnosis and Treatment、Endoplasmic Reticulum Stress and Disease、Pancreatic function and diabetes

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 discriminat...