Gene Identification in Non-Alcoholic Fatty Liver Disease

 

 

Relevance to SWEHSC: 

Dr. Cherrington identified critical genes and gene networks involved in fatty liver disease. Gene expression results created the need for access to enhanced cell imaging techniques in order to localize the cellular compartments to which proteins from the identified mRNAs localized, which was facilitated by the Imaging FC. 

Cluster of Efforts: 

Investigators: 

  • Nathan Cherrington, PhD.
Milestones: 
  • Identified critical genes and gene networks involved in fatty liver disease. 
  • In this study expression profiling data from normal, steatosis, and NASH human livers were used to predict transcription factors that are misregulated as mechanistic features of NAFLD progression.
  • Previously-published human NAFLD gene expression profiling data from normal, steatosis, and NASH livers were subjected to transcription factor binding site enrichment analysis. 
  • Selected transcription factors that bind enriched transcription factor binding sites were analyzed for changes in expression.
  • Distinct transcription factor binding sites were enriched in genes significantly up- or down-regulated in NASH livers.
  • Those enriched in up-regulated genes were bound by transcription factors such as FOXA, CEBP, and HNF1 family members, while those enriched in down-regulated genes were bound by nuclear receptors involved in xenobiotic sensing and lipid metabolism.
  • Levels of mRNA and protein for selected transcription factors were significantly changed during disease progression. The study indicates that NAFLD progression involves changes in activity or expression of transcription factors that regulate genes involved in hepatic processes known to be altered in NASH.
  • Transcription factors such as PPAR receptors, FoxA family members, and HNF4A might be targeted therapeutically to prevent NAFLD progression.
  • Gene expression results created the need to access for access to enhanced cell imaging techniques in order to localize cellular compartments to which proteins from the identified mRNAs localized. 
People Terms: 
SWEHSC Terms: