Identification of key pathways and genes in nonalcoholic fatty liver disease using bioinformatics analysis

Abstract

A b s t r a c t Introduction: Nonalcoholic fatty liver disease (NAFLD) is one of the most common types of liver disease in the world. However, the molecular mechanisms regulating the development of NAFLD have remained unclear. Material and methods: In the present study, we analyzed two public datasets (GSE48452 and GSE89632) to identify differentially expressed mRNAs in the progression of NAFLD. Next, we performed bioinformatics analysis to explore key pathways underlying NAFLD development. Results: Gene Ontology (GO) analysis showed that differentially expressed genes (DEGs) were mainly involved in regulating a series of metabolism-related pathways (including proteolysis and lipid metabolism), cell proliferation and adhesion, the inflammatory response, and the immune response. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that DEGs in NAFLD were mainly enriched in the insulin signaling pathway, peroxisome proliferator-activated receptor (PPAR) signaling pathway, and p53 signaling pathway. We also constructed protein-protein interaction (PPI) networks for these DEGs. Interestingly, we observed that key hub nodes in PPI networks were also associated with the progression of hepatocellular carcinoma (HCC). Conclusions: Taken together, our analysis revealed that a series of pathways, such as metabolism and PPAR signaling pathways, were involved in NAFLD development. Moreover, we observed that many DEGs in NAFLD were also dysregulated in HCC. Although further validation is still needed, we believe this study could provide useful information to explore the potential candidate biomarkers for diagnosis, prognosis, and drug targets of NAFLD.

Construction and Analysis of Protein-Protein Interaction Network of Non-Alcoholic Fatty Liver Disease

“…Interestingly, several studies applying bioinformatics analyses are in consistensy with our findings, revealing the possible implication of UBQLN4 [80], UBC [81] and PCNA [82] in NAFLD development as potential biomarkers. Likewise, a bioinformatics analysis in a PPI network of steatosis highlights CRK and MDM2 among of the top 10 important genes [83].…”

Palmitate and Fructose Interact to Induce Human Hepatocytes to Produce Pro-Fibrotic Transcriptional Responses in Hepatic Stellate Cells Exposed to Conditioned Media

“…In humans, fructose consumption for ten weeks led to increased hepatic de novo lipogenesis and 23-hour postprandial hypertriglyceridemia [14], suggesting that fructose may contribute to the development of NAFLD via the circulating lipid pool [8]. These data are consistent with recent evidence indicating that transcriptomic changes accompanying the early development of NAFLD occur predominantly in hepatocytes [24]. To date, however, the impact of palmitate-and fructose-treated human hepatocytes on transcriptomic changes in HSCs has not yet been characterized.…”

“…A number of studies have investigated changes in intercellular metabolism resulting from exposure to these nutrients in primary or immortalized hepatocytes and hepatic stellate cells (HSCs) [20][21][22][23][24][25][26][27][28]. HSCs are quiescent under physiological conditions, but are activated to a myofibroblastic state in response to injurious stimuli, whereupon they begin to secrete cytokines and components of the extracellular matrix (ECM).…”

Kaempferol Alleviates Steatosis and Inflammation During Early Non-Alcoholic Steatohepatitis Associated With Liver X Receptor α-Lysophosphatidylcholine Acyltransferase 3 Signaling Pathway

“…Primary cells have not been used to build cell models. In a bioinformatics analysis study on NAFLD, it is mentioned that the occurrence of NAFLD is also related to insulin signaling pathway, PPAR signaling pathway, p53 signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway ( Liu et al, 2020 ). The study found that giving p53 knockout mice a high-fat diet reduced the occurrence of NAFLD.…”