OBJECTIVETo determine the role of zinc finger protein 1 (ZEB 1) in liver fibrosis and in regards to expression of the tumor growth factor-beta (TGFb) signaling factor using a rat model system.

METHODSSprague-Dawley rats were randomly divided into a normal (control) group, liver fibrosis (model) group and a liver fibrosis + therapy (ZEB1 intervention) group. The model group and the ZEB1 intervention group were given intraperitoneal injections of dimethylnitrosamine (DMN) for the first 3 days of each week over a 7-week period; starting at week 5, the ZEB 1 intervention group was started on a routine of every other day tail vein injections of recombinant ZEB1. During this 7-week period, the control group was given intraperitoneal injections of 0.9% NaC1 alone on the DMN schedule. Liver tissues were collected for pathological examination (with hematoxylin-eosin and Masson staining) and for detection of TGFb1 and ZEB 1 expression (by RT-PCR and western blotting). Measurement data were compared between groups using the single-factor analysis of variance test, followed by the least significant difference LSD test. Count data were analyzed by Fisher's exact test.

RESULTSThe model group's liver tissues showed degeneration and necrosis, as well as obvious fibrous septa accompanied by pseudo lobules. The ZEB 1 intervention group's liver tissues showed a significantly higher degree of fibrosis (x²=21.63, P=0), with more coarse fiber cords. The expression of ZEB1 and TGFb1 was significantly higher in the model group than in the control group (both P less than 0.05). However, the ZEB 1 intervention group showed the highest levels of ZEB 1 and TGFb1 expression (vs. model group, P less than 0.05).

CONCLUSIONZEB 1 may promote the development of liver fibrosis in rats through a mechanism involving the TGFb/Smad signaling pathway.