Effects of Kudoa septempunctata infections in a human intestinal epithelial model (Caco-2): a DNA microarray study

Figures & data

Figure 1. Transepithelial electrical resistance (TER) in a Caco-2 cell monolayer, and heatmap of the differentially expressed genes as identified by microarray data.

Table 1. GO terms in the deepest level of hierarchy and genes significantly up/down regulated by K. septempunctata infection (FDR<0.05, Benjamini<0.05). Gene title list addressed in S1 Table.

GO ID	GO terms (Biological Process)	Gene regulated	Gene symbol
0006915	apoptotic process	up	ADM, AKIP1///NUAK2, ANXA1, BCL6, BCL10, BIRC3, BTG2,
			C8orf4, CSRNP1, CTGF, CYR61, DCUN1D3, DDIT3, DUSP1, DUSP6,
			EGR1, EGR3, EGR4, EPHA2, FOSL1, GADD45A, GADD45B, GDF15
			ID1, ID3, IER3, JUN, KLF4, LOC728392, MAP3K14, MCL1, NFKBIA
			NR4A1, NR4A2, NR4A3, PHLDA1, PLK3, PMAIP1, PPP1R15A, RGCC
			RHOB, SERPINE1, TNFAIP3, ZFP36L1
		down	ALB, API5, DNASE1, FGA, API5, DNASE1, FGA, GPLD1, HIP1,
			HMGA2, OGT, PTK2, S100A9, SRC, UBE2D3
0043065	positive regulation of apoptotic process	up	ADM, ANXA1, BCL6, BCL10, CYR61, DCUN1D3, DUSP1, DUSP6
			FOSL1, GADD45A, GADD45B, ID3, JUN, NR4A1, PHLDA1, PMAIP1,
			RHOB
		down	GPLD1, HMGA2, SRC
0002237	response to molecule of bacterial origin	up	BCL10, CXCL2, CXCL8, TNFAIP3
0009612	response to mechanical stimulus	up	BCL10, BTG2, EGR1, FOS, FOSB, FOSL1, GADD45A, JUN, JUNB
			MAP3K14, RCAN1
		down	SRC
0032870	cellular response to hormone stimulus	up	CGA, DUSP1, FOS, FOSB, JUN, JUNB
0034097	response to cytokine	up	FOS, FOSL1, JUN, JUNB, KLF4, MCL1, OSMR, SRF
		down	FGA
0042542	response to hydrogen peroxide	up	ANXA1, AREG, DUSP1, FOSL1, JUN, KLF2, KLF4, KLF6, ND6,
			NR4A3, PPP1R15B, RHOB, TNFAIP3
		down	SRC
0051591	response to cAMP	up	AREG, DUSP1, EGR1, EGR3, EGR4, FOS, FOSB, FOSL1, JUN, JUNB
			PER1
		down	AKAP9, SLC26A3
1901653	cellular response to peptide	up	ID1, KLF2, KLF4, KLF6, KLF10
		down	SRC
0035914	skeletal muscle cell differentiation	up	ATF3, BTG2, EGR1, EGR2, FOS, MAFF, NR4A1
0000122	negative regulation of transcription from RNA	up	ATF3, BCL6, BHLHE40, BTG2, DDIT3, DLX2, EGR1, ETS2, FOSB
	polymerase II promoter		ID1, ID3, JUN, JUNB, KLF4, KLF10, SIK1,
			MXD1, NR4A2, NR4A3, OSR2, OVOL1, PER1, PER2, PLK3,
			PPP1R15A, USP2, ZFP36
		down	HMGA2, N4BP2L2, PPARA, RBL1, UBE2D3, ZMYND8
0008285	negative regulation of cell proliferation	up	ADM, BCL6, BTG2, CXCL8, EREG, FOSL1, ING1, JUN, KLF4, KLF10
			SIK1, RGCC, SRF, TOB2
		down	CNOT7, GPLD1
0045944	positive regulation of transcription from RNA	up	ATF3, BTG2, CGA, CSRNP1, CYR61, DDIT3, DLX2, EGR1, EGR2,
	polymerase II promoter		ELF3, ETS2, FOS, FOSB, FOSL1, ITGA8, JUN, JUNB, KLF2, KLF4,
			KLF6, SIK1, MAFF, NFKBIA, NR4A1, NR4A2,
			NR4A3, OSR2, PER1, RGCC, SERPINE1, SERTAD1, SRF
		down	CNOT7, CRTC3, HMGA2, HNF1A, MED6, OGT, PPARA, RBL1, TFEC
0051726	regulation of cell cycle	up	C8orf4, FOSL1, GADD45A, GADD45B, ID3, JUN, JUNB, NR4A1,
			NR4A3, PER2, RGCC, RHOB, WEE1
		down	HMGA2, RBL1, SRC
0000188	inactivation of MAPK activity	up	DUSP1, DUSP2, DUSP4, DUSP5, DUSP6, RGS3
0001706	endoderm formation	up	DUSP1, DUSP2, DUSP4, DUSP5
0015721	bile acid and bile salt transport	down	AKR1C1///AKR1C2, ALB, SLC51A
0007623	circadian rhythm	up	BHLHE40, EGR1, EGR3, ID1, ID3, JUN, KLF10, PER1, PER2,
			SERPINE1
		down	MTTP, PPARA

Table 2. A list of biological process Gene Ontology (GO) terms of “cell adhesion” and “tight junction” and their component genes by K. septempunctata infection (FDR<0.05, Benjamini<0.05).

GO terms	Gene Symbol	Gene regulated	Gene Title
Cell adhesion	CDHR5	down	cadherin-related family member 5
	CEACAM1		carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein)
	COL12A1		collagen, type XII, alpha 1
	FGA		fibrinogen alpha chain
	FN1		fibronectin 1
	PPARA		peroxisome proliferator-activated receptor alpha
	PTK2		protein tyrosine kinase 2
	SRC		SRC proto-oncogene, non-receptor tyrosine kinase
	CTGF	up	connective tissue growth factor
	CXCL8		chemokine (C-X-C motif) ligand 8
	CYR61		cysteine-rich, angiogenic inducer, 61
	EPHA2		EPH receptor A2
	ITGA8		integrin alpha 8
	KLF4		Kruppel-like factor 4 (gut)
	MYADM		myeloid-associated differentiation marker
	RGCC		regulator of cell cycle
	RHOB		ras homolog family member B
	RND1		Rho family GTPase 1
	SERPINE1		serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1
	SRF		serum response factor
Tight junction	FRMD4A	down	FERM domain containing 4A

Table 3. The enriched KEGG pathway of K. septempunctata infection.

KEGG entry ID	KEGG pathway	Annotated gene number	P-Value
hsa04010	MAPK signaling pathway	13	0.002
hsa04668	TNF signaling pathway	8	0.003
hsa05166	HTLV-I infection	12	0.005
hsa04064	NF-kappa B signaling pathway	6	0.018
hsa04380	Osteoclast differentiation	7	0.028
hsa05202	Transcriptional misregulation in cancer	8	0.029
hsa05120	Epithelial cell signaling in Helicobacter pylori infection	5	0.030
hsa05161	Hepatitis B	7	0.043

Figure 2. Heat map of inflammation-related genes.

Figure 3. Mapping of the extracted gene products in pathways stimulated by K. septempunctata invasion.

Figure 4. Effect of incubation with K. septempunctata on IL-8 and 5-HT production by Caco-2 cell monolayers.