Gene expression profiles of hepatic cell-type specific marker genes in progression of liver fibrosis

Table 2 Marker genes for hepatocytes that showed a strong relationship with fibrogenesis

Functional category	Cluster No.	Direction of change	Annotation	Symbol	Common
Amino acid metabolism	7	Increase	Glutamate oxaloacetate transaminase 1	Got1	J04171
	7	Increase	Glutamic-pyruvate transaminase (alanine aminotransferase)	Gpt	D10354
	9	Increase	Glutathione-S-transferase, alpha type2	Gsta2	AA945082
	3	Decrease	Cytosolic cysteine dioxygenase 1	Cdo1	AA942685
	10	Decrease	Cysteine-sulfinate decarboxylase	Csad	M64755
Cholesterol synthesis	3	Decrease	Nuclear receptor subfamily 0, group B, member 2	Nr0b2	D86745
Steroid hormone synthesis	7	Increase	Hydroxysteroid (17-beta) dehydrogenase 9	Hsd17b9	U89280
	7	Increase	(20-alpha-hydroxysteroid dehydrogenase)	---	AA866264
	1	Decrease	Hydroxysteroid (17-beta) dehydrogenase 2	Hsd17b2	X91234
	3	Decrease	Sulfotransferase, estrogen preferring	Ste	S76489
Lipid biosynthesis, metabolism, fatty acid & lipid transport	9	Increase	Carboxylesterase 2 (intestine, liver) (drug metabolism)	Ces2	AB010635
	1	Decease	2-hydroxyphytanoyl-CoA lyase(peroxisomal) alpha-oxidation	Hpcl2	AA893239
	3	Decease	Carboxylesterase 3	Ces3	L46791
	3	Decease	Hydroxyacid oxidase 2 (long chain)(peroxisomal)( alpha-oxidation)	Hao2	AI232087
	3	Decease	Fatty acid binding protein 7, brain (cytosolic)	Fabp7	U02096
	10	Decease	Alpha-methylacyl-CoA racemase Peroxisomal)	Amacr	U89905
Retinoid synthesis & metabolism	3	Decease	Retinol dehydrogenase type II (RODH II)	RoDHII	U33500
	10	Decease	Retinol dehydrogenase type III	Rdh3	U18762
Dlucolysis & gluconeogenesis	7	Increase	Glucokinase	Gck	X53588
	3	Decrease	Phosphoenolpyruvate carboxykinase 1(PEPCK1) (cytosolic)	Pck1	K03243
	3	Decrease	Pyruvate carboxylase	Pc	U32314
	3	Decrease	Solute carrier family 37 (glycerol-6-phosphate transporter), member 4	Slc37a4	AF080468
	3	Decrease	Ribonuclease, RNase A family 4	Rnase4	AF041066
	3	Decrease	Ectonucleotide pyrophosphatase/phosphodiesterase 2(lysophospholipaseD)	Enpp2	D28560
Drug-metabolism	7	Increase	Cytochrome P450, family 3, subfamily a, polypeptide 13	Cyp3a13	U46118
	9	Increase	Aldehyde dehydrogenase family 1, member A1	Aldh1a1	AF001898
	1	Decrease	Cytochrome P450, family 1, subfamily a, polypeptide 2	Cyp1a2	E01184
	1	Decrease	Cytochrome P450, subfamily IIC (mephenytoin 4-hydroxylase)	Cyp2c	X79081
	1	Decrease	Flavin containing monooxygenase 1	Fmo1	M84719
	3	Decrease	Cytochrome P450, family 17, subfamily a, polypeptide 1	Cyp17a1	M21208
	3	Decrease	Cytochrome P450, family 3, subfamily a, polypeptide 11	Cyp3a11	M13646
	3	Decrease	Alcohol dehydrogenase 4 (class II), pi polypeptide	Adh4	X90710
	3	Decrease	3-hydroxybutyrate dehydrogenase (heart, mitochondrial)	Bdh	AA817846
	3	Decrease	Camello-like 1 N-acetyltransferase 8, NAT8)	Cml1	AA892382
	3	Decrease	(hydroxysteroid sulfotransferase )	---	M31363
	3	Decrease	(hydroxysteroid sulfotransferase subunit)	---	AA818122
Growth factors & their receptors	7	Increase	Lipopolysaccharide binding protein	Lbp	L32132
	9	Decrease	Insulin-like growth factor binding protein 2	Igfbp2	J04486
	3	Decrease	Activin beta E	Inhbe	AF089825
	10	Decrease	Growth hormone receptor	Ghr	S49003
	10	Decrease	Insulin-like growth factor binding protein 1	Igfbp1	M58634
	10	Decrease	Deiodinase, iodothyronine, type I	Dio1	X57999
Hepatic secretory proteins	7	Increase	Alpha-fetoprotein	Afp	X02361
	1	Decrease	Alpha-2u globulin PGCL4 /// alpha-2u globulin PGCL2 /// alpha-2u-globulin (L type)/// alpha-2u globulin PGCL1 /// alpha-2u globulin PGCL3	Obp3 /// LOC298109 /// LOC298116 /// LOC259246 /// LOC259244	M27434
	1	Decrease	Alpha-2u globulin PGCL4 (Ppp2r2a protein phosphatase 2 (formerly 2A), regulatory subunit B (PR 52), alpha isoform)	Obp3	J00738
	10	Decrease	Metallothionein	Mt1a	AI102562
Protease & protease inhibitor	9	Increase	Lipocalin 2	Lcn2	AA946503
	1	Decrease	Elastase 1, pancreatic	Ela1	L00117
	10	Decrease	Esterase 2 (liver carboxylesterase)	Es2	M20629
	3	Decrease	Serine protease inhibitor	Spin2a	D00752
Cell surface proteins & structural proteins	7	Increase	Keratin complex 2, basic, gene 8 (cytokeratin-8)	Krt2-8	S76054
	7	Increase	Similar to cytokeratin(keratin complex 1, acidic, gene 18)	(Krt1-18)	AI072634
Signal transduction	3	Decrease	Regucalcin	Rgn	D31662
Transporters	7	Increase	solute carrier family 17 (sodium phosphate), member 1	Slc17a1	U28504
	7	Increase	Aquaporin 7	Aqp7	AB000507
	9	Increase	ATP-binding cassette, sub-family B (MDR/TAP), member 1	Abcb1	M81855
	3	Decrease	Solute carrier family 10 (sodium/bile acid cotransporter family), member 1	Slc10a1	M77479
Protein related vitamins	10	Decrease	L-gulono-gamma-lactone oxidase	Gulo	D14564
Others	7	Increase	Rabphilin 3A-like (without C2 domains)	Rph3al	AF022774
	1	Decrease	Carbonic anhydrase 3	Ca3	AF037072

Gene expression profiles in the chronic phase (d 7, 14, 21 and 28) were clustered into 10 patterns using K-means analysis. Clustered genes that showed a tendency to temporally decrease (clusters 1, 3 and 10) or increase (clusters 7 and 9) were selected, as shown in Table 1 in the supplemental data. Among these genes, those showing a strong relation with fibrogenesis were further selected based on a t-test statistical analysis of the rate of change in expression intensity and the number of days of fibrosis. Hepatocyte-specific gene markers showing a strong relation with fibrogenesis are listed.