Crucial role of SDF-1/CXCR4 interaction in the differentiation of hepatic oval cells

doi:10.3877/cma.j.issn.1674-0793.2008.03.006

Abstract

Abstract:

Objective

To investigate the mechanism of SDF-1/CXCR4 biological axis in the activation,proliferation and differentiation of hepatic oval cell.

Methods

Compared with three control groups (two-thirds hepatectomy. Two-thirds hepatectomy with AMD3100,two-thirds hepatectomy with 2-acetylaminoflunzene and AMD3100),the pathological changes of oval cells of experiment group(two-thirds hepatectomy with 2-acetylaminoflunzene)were observed by light and transmission electron microscope in the different period(3,5,7,10,14，21 days after surgery).CK18,CK19,AFP,SDF-1 and CXCR4 protein were continuously detected by immuno-histochemistry stainging,SDF-1 mRNA and CXCR4 mRNA were measured by RT-PCR.

Results

In the AAF/PH model, from 3 to 10 days after surgery,CK18, CK19,AFP, SDF-1 and CXCR4 protein expression positive cells progressively increased with time.SDF-1 and CXCR4 expressed on biliary cells lining interlobour bile ducts and oval cells which adjectent to proliferent bile duct cells. From 10 to 14 days after surgery,CK18,CK19,AFP,SDF-1 and CXCR4 protein expression positive cells increased to reach a maximal intensity and decreased thereafter,which decreased to reach a minimal intensity at day 21 after surgery.

Conclusion

The SDF-1/CXCR4 biological axis plays a role in oval cell accumulation in the differentiation of hepatic oval cells, SDF-1 and its receptor CXCR4 might be important markers of hepatic stem cells.

Key words: Hepatic stem cells, Oval cells, SDF-1, CXCR4

Xing-yuan JIAO, San-ping ZENG, Xiao-ming HUANG, Yi-ze HU, Can-qiao LUO, Jun DU, Jin-lang WU. Crucial role of SDF-1/CXCR4 interaction in the differentiation of hepatic oval cells[J]. Chinese Archives of General Surgery(Electronic Edition), 2008, 02(03): 190-196.

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Figures/Tables 17

References 13

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分组	CK18	CK19	AFP	SDF-1	CXCR4
AAF/AMD3100/PH
3d	8.42±1.97	8.25±1.86	7.75±1.85	10.04±1.64	11.56±1.66
5d	6.11±1.86	6.24±1.73^#	5.84±1.97^#	7.36±1.71^#	8.39±1.68^#
7d	4.22±1.87^#	4.26±1.68^#	2.99±1.86^#	5.08±1.68^#	6.10±1.69^#
10～21d	0	0	0	0	0
AAF/PH
3d	9.36±1.91^☆	9.38±1.62^*	8.32±1.63^*	11.44±1.67	12.48±1.58
5d	15.07±1.82^#☆	15.12±1.67^#☆	14.71±1.84^#☆	15.35±1.93^#☆	16.99±1.88^#☆
7d	18.01±1.84^#☆	18.28±1.33^#☆	17.24±1.94^#☆	19.28±1.92^#☆	20.48±2.08^#☆
10d	25.01±1.92^#☆	24.25±1.89^#☆	26.43±2.02^#☆	24.56±1.87^#☆	25.36±1.93^#☆
14d	24.00±1.96^#☆	24.18±1.74^#☆	16.57±1.98^#☆	23.54±1.75^#☆	19.42±1.83^#☆
21d	6.22±1.99^#☆	6.43±1.71^#☆	3.23±2.03^#☆	4.57±1.96^#☆	7.65±1.85^#☆

分组	CK18	CK19	AFP	SDF-1	CXCR4
AAF/AMD3100/PH
3d	8.42±1.97	8.25±1.86	7.75±1.85	10.04±1.64	11.56±1.66
5d	6.11±1.86	6.24±1.73^#	5.84±1.97^#	7.36±1.71^#	8.39±1.68^#
7d	4.22±1.87^#	4.26±1.68^#	2.99±1.86^#	5.08±1.68^#	6.10±1.69^#
10～21d	0	0	0	0	0
AAF/PH
3d	9.36±1.91^☆	9.38±1.62^*	8.32±1.63^*	11.44±1.67	12.48±1.58
5d	15.07±1.82^#☆	15.12±1.67^#☆	14.71±1.84^#☆	15.35±1.93^#☆	16.99±1.88^#☆
7d	18.01±1.84^#☆	18.28±1.33^#☆	17.24±1.94^#☆	19.28±1.92^#☆	20.48±2.08^#☆
10d	25.01±1.92^#☆	24.25±1.89^#☆	26.43±2.02^#☆	24.56±1.87^#☆	25.36±1.93^#☆
14d	24.00±1.96^#☆	24.18±1.74^#☆	16.57±1.98^#☆	23.54±1.75^#☆	19.42±1.83^#☆
21d	6.22±1.99^#☆	6.43±1.71^#☆	3.23±2.03^#☆	4.57±1.96^#☆	7.65±1.85^#☆

分组	SDF-1	CXCR4
AAF/AMD3100/PH
3d	35.25±10.05	30.76±10.14
5d	25.26±9.89^#	23.31±9.69^#
7d	15.13±10.07^#	14.08±9.44^#
10～21d	0	0
AAF/PH
3d	34.43±10.21	31.28±9.82
5d	44.28±9.89^#☆	41.34±10.15^#☆
7d	58.21±10.17^#☆	57.18±10.18^#☆
10d	105.18±10.90^#☆	95.45±9.98^#☆
14d	97.22±9.76^#☆	89.36±11.29^#☆
21d	66.47±9.68^#☆	55.29±9.84^#☆

分组	SDF-1	CXCR4
AAF/AMD3100/PH
3d	35.25±10.05	30.76±10.14
5d	25.26±9.89^#	23.31±9.69^#
7d	15.13±10.07^#	14.08±9.44^#
10～21d	0	0
AAF/PH
3d	34.43±10.21	31.28±9.82
5d	44.28±9.89^#☆	41.34±10.15^#☆
7d	58.21±10.17^#☆	57.18±10.18^#☆
10d	105.18±10.90^#☆	95.45±9.98^#☆
14d	97.22±9.76^#☆	89.36±11.29^#☆
21d	66.47±9.68^#☆	55.29±9.84^#☆

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