Table 2.
Modulation of gene expression in human liver cell models after treatment with PPARγ agonists.
Ref. | [34] | [35] | [65] | Rogue et al. unpublished | [74] | [75] | [76] | [77] | [78] | [79] | [80] | [81] | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
model | PHH | PHH DONOR 1 | PHH DONOR 2 | PHH DONOR 3 | PHH DONOR 4 | PHH DONOR 5 | HepaRG cells | HepaRG cells | Hep3b Huh7 | Huh7 | Hepg2 | HLF | HLF, HAK, HuH-7 | ||||||||||||||
treatment | TRO 24 h 5,50,100 μM- |
TRO 24 h 25 μM- | TRO 24 h 10 μM- | TRO 24 h 5 μM- | TRO 24 h 20 μM- | TRO 24 h 5 μM- | TRO 24 h 20 μM- | TRO 24 h 5 μM- | TRO 24 h 20 μM- | TRO 24 h 5 μM- | TRO 24 h 20 μM- | TRO 24 h 40 μM- | TRO 24 h 5 μM- | TRO 24 h 20 μM- | TRO 24 h 40 μM- | TRO 24 h 5 μM- | TRO 24 h 20 μM- | TRO 24 h 40 μM- | TRO 24 h 0,024 μM–25 μM | TRO04 8 h - 50 μM- |
TRO-ROSI 1–8– 24 h 50 μM- |
TRO 6 h 30 μM- | TRO-4 h 10–30 μ M | TRO-ROSI 48 h 25–100 μM- | TRO for up 48 h 50 μM | TRO 24 h 50 μM | |
method | q-PCR | Amer-sham | Agilent | Agilent | q-PCR | Super Array Bioscience qPCR | q-PCR/ northern blotting | q-PCR | |||||||||||||||||||
ABCB1 | + | 0 | + | 0 | 0 | + | + | 0 | 0 | + | + | + | + | 0 | 0 | 0 | |||||||||||
Transporters | ABCC2 | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | + | 0 | 0 | 0 | ||||||||||
ABCC3 | + | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
SLC10A1 | − | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | − | − | − | |||||||||||
ABCB4 | + | 0 | 0 | 0 | 0 | + | + | 0 | + | + | + | + | + | 0 | 0 | 0 | |||||||||||
SLCO1B1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | |||||||||||
SLCO1B3 | − | − | − | − | − | − | − | 0 | − | − | 0 | − | − | 0 | 0 | 0 | |||||||||||
| |||||||||||||||||||||||||||
CCND1 | + | 0 | + | + | + | 0 | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
Cell cycle, proliferation, death and differentiation | CDKN1A | 0 | 0 | 0 | + | + | + | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | + | + | ||||||||
GADD45G | + | 0 | + | 0 | 0 | 0 | + | 0 | 0 | 0 | + | + | + | 0 | 0 | 0 | |||||||||||
AFP | − | 0 | − | 0 | − | 0 | 0 | 0 | − | − | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
TGFA | + | 0 | 0 | 0 | − | − | − | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
CCNE1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | + | 0 | 0 | ||||||||||
ALB | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | |||||||||||
CDKN1B | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||||||||||
JUND | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
CCNG1 | 0 | 0 | 0 | − | − | 0 | − | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
MYC | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
TGFB1 | 0 | 0 | 0 | + | + | 0 | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
ALPL | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | + | 0 | 0 | 0 | 0 | 0 | − | |||||||||||
GADD45A | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
IGFBP1 | 0 | 0 | 0 | − | − | − | 0 | 0 | 0 | 0 | + | 0 | 0 | 0 | + | + | |||||||||||
SKP2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | + | − | |||||||||||
| |||||||||||||||||||||||||||
FABP1 | + | + | + | + | + | + | + | 0 | + | + | + | + | + | + | 0 | − | |||||||||||
Lipid metabolism | FASN | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | + | + | 0 | 0 | 0 | 0 | ||||||||||
CPT1A | + | 0 | + | + | + | 0 | 0 | 0 | + | + | + | + | + | 0 | 0 | 0 | |||||||||||
SREBF2 | + | 0 | 0 | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | |||||||||||
HMGCR | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | − | |||||||||||
INSIG1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | + | + | + | 0 | 0 | 0 | nd | |||||||||||
LDLR | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | |||||||||||
INSIG2 | 0 | 0 | 0 | 0 | 0 | − | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | + | |||||||||||
| |||||||||||||||||||||||||||
CYP1A1 | 0 | + | + | 0 | 0 | 0 | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | 0 | 0 | ||||||||||
Xenobiotic metabolism | CYP1A2 | + | 0 | 0 | 0 | − | 0 | 0 | 0 | 0 | 0 | + | 0 | 0 | + | 0 | 0 | 0 | 0 | ||||||||
CYP2B6 | + | + | + | 0 | 0 | + | + | 0 | + | + | 0 | 0 | + | 0 | 0 | 0 | + | ||||||||||
CYP2C9 | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | + | + | + | + | + | 0 | 0 | |||||||||||
CYP2E1 | + | 0 | 0 | − | − | − | − | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | |||||||||||
CYP3A4 | + | + | 0 | 0 | 0 | 0 | + | + | 0 | + | + | + | + | + | + | + | + | + | |||||||||
UGT1A10 | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
GSTP1 | + | 0 | 0 | 0 | 0 | − | − | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
GSTA1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | |||||||||||
G6PC | 0 | 0 | 0 | 0 | − | − | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | − | ||||||||||||
Carbohydrate metabolism | PDK4 | − | 0 | − | − | − | − | 0 | + | + | + | + | + | 0 | + | + | |||||||||||
PEPCK | 0 | 0 | 0 | 0 | − | − | 0 | 0 | 0 | 0 | 0 | + | + | + | + | ||||||||||||
FBP1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | |||||||||||
| |||||||||||||||||||||||||||
HMOX1 | + | + | + | + | + | + | + | + | + | + | 0 | 0 | 0 | 0 | + | + | |||||||||||
Oxidative stres | PTGS2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | − | |||||||||
HSPA1A | + | + | + | 0 | 0 | + | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
TXN | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
COX-2 | − | ||||||||||||||||||||||||||
CAT | − | 0 | 0 | − | − | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | + | |||||||||||
| |||||||||||||||||||||||||||
HNF4A | + | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
Transcription factors | PPARG | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | + | 0 | |||||||||
CEBPA | 0 | 0 | + | + | + | + | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
CEBPB | 0 | 0 | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
NR1I2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
NR1I3 | 0 | 0 | 0 | 0 | − | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | |||||||||||
| |||||||||||||||||||||||||||
GSN | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | |||||||||||
Fbrosis/ senescence |
TIMP1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | ||||||||||
CDH1 | + | + | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | 0 | 0 | 0 | |||||||||||
RGN | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | |||||||||||
| |||||||||||||||||||||||||||
PDIA4 | 0 | 0 | − | − | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | + | |||||||||||
Miscellaneous | ACTA1 | 0 | + | 0 | + | + | 0 | 0 | 0 | 0 | 0 | 0 | 0 | − | 0 | 0 | 0 |
+: up-regulated
−: down-regulated
0: not modulated
The case is empty when the gene has not been studied.
Differentiated HepaRG cells from three different passages and 2-day human hepatocyte cultures from 5 donors were treated for 24 h with different concentrations of TRO. 500 ng of RNA samples from control and treated cultures were separately reverse transcribed and amplified using Quick Amplification Labeling Kit (Agilent). Then they were hybridized using 4×44 K Agilent microarrays satisfying Minimum Information About a Microarray Experiment (MIAME) requirements as previously described [82]. Normalization algorithms and background subtractions were automatically applied to each array to reduce systematic errors and to adjust effects due to technological rather than biological variations using FE and Resolver softwares. The combination of technical and biological replicates uses the error-weighted log ratio average and an estimated error method of the Rosetta Resolver system.