Perturbation of Wnt/β‐catenin signaling and sexual dimorphism in non‐alcoholic fatty liver disease

Autor: Matthew M Yeh, Xiuhui Shi, Jingxuan Yang, Min Li, Kar‐Ming Fung, Sayed S. Daoud
Rok vydání: 2022
Předmět:
Zdroj: Hepatology Research. 52:433-448
ISSN: 1872-034X
1386-6346
DOI: 10.1111/hepr.13754
Popis: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH) is higher in postmenopausal women than men. The aim of this study was to determine the molecular mechanisms underlying this sexual dimorphism in NAFLD.A total of 24 frozen liver samples of both sexes (normal and NAFLD/NASH) were used in this study. Total RNAseq was first used to identify differentially expressed genes (DEGs) between samples. Enrichment analysis of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome were used to analyze biological pathways. RTWe identified 4362 genes that are differentially expressed between NAFLD/NASH and normal samples; of those 745 genes were characterized as sex specific in NAFLD/NASH. Multiple pathway analysis platforms showed that Wnt-signaling is a candidate shared for a common biological pathway-associated with NAFLD/NASH. Using Wnt pathway focused PCR array we identified many genes involved in canonical pathway (Wnt/β-catenin activation) such as CTNNB1, c-Myc and CCND2 are overexpressed in female cases, whereas these genes are either not detected or downregulated in male cases. Immunoblot analysis validated the expression of CTNNB1 in female cases but not in male protein samples.Our study suggests, for the first time, that the activation of canonical Wnt signaling could be one of the main pathways associated with sexual dimorphism in NAFLD and NASH.
Databáze: OpenAIRE
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