[Effects of interferon-alpha on the mRNA expression of procollagen type I and III of hepatic stellate cells and on the deposition of collagen type I and III in fibrotic liver of rats].

OBJECTIVE

To observe the effects of interferon-alpha on the proliferation and mRNA expression of procollagen type I and III and on the deposition of collagen type I and III in fibrotic liver of rats.

METHODS

CCl4 was used to induce the liver fibrosis rat model. The stellate cells were isolated from liver and cultured in DMEM medium. The effects of interferon-alpha on the proliferation and collagen synthesis of stellate cells were determined with 3H-TdR, 3H-proline incorporating test. Total RNA of stellate cells was extracted and the cDNA of procollagen type I and III and of interstitial collagenase was labeled using Dig High Primer technique. The level of procollagen type I and III and interstitial collagenase mRNA were measured by Northern blot analysis. Deposition of collagen type I and III in fibrotic liver was evaluated with Dot blot.

RESULTS

At the 4th, 24th and 48th hour, interferon-alpha inhibited the intake of 3H-TdR and 3H-proline by stellate cells significantly. The inhibition rates were 16%, 19% and 27%, respectively. The intensity of inhibition was proportional to the concentration of interferon-alpha. The expression level of procollagen type I and III mRNA in the interferon-alpha treated group was significantly lower than that in control group in all stages of fibrosis. At the 2nd and 6th week, the deposition of collagen type I and III in interferon-alpha treated group decreased significantly compared with that in control group. However, no difference was found at the 9th week. The expression of collagenase mRNA between interferon-alpha treated group and control group showed no difference.

CONCLUSION

Interferon-alpha can inhibid the proliferation and collagen synthesis of stellate cells, down-regulate the expressions of procollagen type I and III mRNA and reduce the deposition of collagen type I and III in fibrotic liver. It has no effect on collagenase.