Table 4

Identified master regulators that control inflammatory reprogramming of the liver

Transcription factor

Regulator of/node point for

Example of downstream effects

AP-1 (c-jun/c-fos)

Inflammation

Mmp-12, col1a1, hsp27

CREP binding protein (CBP)

Lipid, inflammation, immune response, cell proliferation

Very broadly acting coactivator (can bind to SREBPs)

C/EBPs

Lipid, inflammation, energy metabolism

Acute phase genes (for SAA, CRP, fibrinogen), hepatic gluconeogenesis and lipid homeostasis, energy metabolism (PEPCK, FAS), TGF-β signaling

Forkhead transcription factor FOXO1

Lipid, inflammation/proliferation

Glycolysis, pentose phosphate shunt, and lipogenic and sterol synthetic pathways, LPL (via SHP)

NF-κB

Inflammation

SAA, CD83, CD86, CCR5, VEGF-C

PPARα/RXRα

Lipid, inflammation

LPL, ABCA1, macrophage activation, glucose homeostasis

p53

Inflammation

HSP27, HSPA4, IFI16, IBP3, RBBP4

SMAD3

Inflammation

Proteases and growth factors (via TGF-β signaling)

SP-1

Lipid, inflammation

ABCA1, ICAM-1, cellular matrix genes COL1A1, COL1A2

SREBP-1/-2

Lipid, inflammation

Sterol biosynthesis genes, LDLR, link to C/EBPα

STAT1/3/5

Inflammation

Acute phase genes

YY1

Inflammation/proliferation

Inflammatory response genes (SAA, vWF, CCR5), cellular matrix genes

Biological networks were generated using MetaCore™ software and transcriptional master regulators were identified in significant gene networks (P < 0.05).

Kleemann et al. Genome Biology 2007 8:R200   doi:10.1186/gb-2007-8-9-r200