[Transforming growth factor β1 cooperates with stromal cell derived factor 1 to affect the proliferation of hepatic oval cells via β-catenin inactivation].

OBJECTIVE

To investigate the role of stromal cell derived factor 1 (SDF-1) on the proliferation of hepatic oval cells, and the influencing factors.

METHODS

Flow cytometry was used to detect the expression of CXCR4 on the cell surface when WB-F344 cells were growing in the culture medium with and without transforming growth factor β1 (TGF-β1) respectively. Western bolt was used to detect the expression of β-catenin and its phosphorylation level. The translocation of β-catenin was shown by confocal microscopy analysis. Q-RT-PCR was used in detecting the β-catenin downstream gene expression such as Ccnd1 and c-Myc. MTT was used to detect the proliferation of WB-F344 cells which were treated by SDF-1 + TGF-β1 and those cells exposed to SDF-1 or TGF-β1 only, as well as of the negative control group.

RESULT

WB-F344 cells rarely express CXCR4 under conventional circumstance, but this receptor can be up-regulated when the culture medium contain a modest amount of TGF-β1 (the rate of CXCR4 positive cell increased by 39.5%). The bond of SDF-1 to CXCR4 results in the phosphorylation of β-catenin, and its inactivation. SDF-1 alone didn't affect the proliferation of WB-F344 cells (0.512 ± 0.010 vs. 0.513 ± 0.008, t = 0.337, P > 0.05), while TGF-β1 group show a slight decrease of cell population (0.393 ± 0.007,t = 28.001, P < 0.05). But when TGF-β1 combined with SDF-1, the proliferation of WB-F344 was more weakened than TGF-β1 group, and the difference was statistically significant (0.272 ± 0.009,t = 32.204, P < 0.05).

CONCLUSIONS

TGF-β1 can up-regulate the expression of CXCR4 in hepatic oval cells, and then inhibit the proliferation of hepatic oval cells via inactivating β-catenin in vitro.