TABLE 2

Mean relative change in mRNA expression, protein levels, and in situ enzyme activity in hepatocytes cultured at different conditions compared with control (ECM overlay, 0.01 μM DEX)

The same donor preparations (n = 3) were used for all of the tested conditions. An analysis of mRNA expression and enzyme activity was performed after 4 days in culture and protein after 5 days, respectively. P450 and UGT proteins were determined from microsomal fractions, and transporter proteins were determined from plasma membrane preparations of hepatocyte cultures.

Target	0.1 μM DEX			Collagen I			Single Gel
Target	mRNA	Protein	Activity	mRNA	Protein	Activity	mRNA	Protein	Activity
CYP1A2	1.58	1.93	1.08	0.74	1.64	0.70	0.53	0.62	0.68
CYP2A6	3.00	2.28		0.38	1.45		0.29	0.45
CYP2B6	1.01		0.93	0.39		0.78	0.27		0.77
CYP2C8	1.27	1.12	1.15	0.75	1.24	0.71	0.49	0.60	0.60
CYP2C9	1.13	1.47	0.98	0.66	1.53	0.49	0.51	0.82	0.75
CYP2C19	0.96	0.80	0.93	0.75	1.43	0.71	0.77	0.79	0.74
CYP2D6	1.19	1.34		0.59	1.60		0.44	0.70
CYP2E1	0.95	2.20		0.49	2.02		0.36	0.98
CYP3A4^*	1.76	1.53	1.66	0.33	0.70	0.57	0.32	0.73	0.88
CYP3A43
CYP3A5	1.51			0.56			0.63
CYP3A7	0.82	16.16		0.42	6.85		0.97	0.92
CYP4A11	0.74	0.89		0.52	1.01		0.53	0.75
P450 reductase
UGT1A1	1.04	1.45		0.68	1.48		0.64	0.89
UGT1A4	1.00			0.62			0.65
UGT1A6	1.25			0.90			0.90
UGT1A9	1.11			0.62			0.73
UGT2B7	0.80	1.03		0.57	1.37		0.65	1.46
UGT2B15	0.54			0.78			0.91
Na/K-ATPase		1.45			1.92			1.02
γ-GTP		3.87			7.64			6.99
β-actin	1.00			1.00			1.00
ABCA8	0.89	0.57		1.04	0.94		0.82	0.63
MDR1	1.42	0.38		1.11	0.69		1.27	0.64
MDR3		0.44			0.49			0.67
BSEP	1.39	0.67		0.49	0.74		0.35	0.66
MRP1	0.67	0.35		0.72	2.29		1.04	0.53
MRP2	1.19	0.53		0.94	0.63		0.59	0.51
MRP3
MRP4
MRP5		0.79			1.55			3.61
MRP6		0.75			0.49			0.79
BCRP	1.17	0.89		0.81	0.90		0.59	0.92
ABCG8	1.38	0.34		0.83	0.51		0.66	0.41
NTCP	1.17	0.84		0.73	0.87		0.58	0.62
OAT2		0.75			1.04			0.75
OCT1	1.92	0.96		0.62	0.69		0.39	0.53
OATP1B3	0.67	0.94		0.51	1.03		0.51	0.89
OATP2B1	1.06	0.93		1.04	1.21		0.65	0.74
OATP1B1	0.76	1.04		0.97	0.95		0.57	0.84
CNT1		0.31			0.63			0.47
ENT1		0.41			0.94			0.60
MCT1		0.54			0.65			0.63
MATE1	1.55	0.57		0.64	0.80		0.79	0.65
Na/K-ATPase		0.70			0.58			0.79
γ-GTP		0.63			0.79			0.94
β-actin	1.00			1.00			1.00

↵* CYP3A4 protein was determined indirectly by CYP3A4 = CYP3A4/CYP3A43 − CYP3A43.