PURPOSE:
The degradation of the
extracellular matrix has been shown to
play an important
role in the
treatment of
hepatic cirrhosis. In this study, the effect of
thalidomide on the degradation of
extracellular matrix was evaluated in a
rat model of
hepatic cirrhosis. MATERIALS AND
METHODS:
Cirrhosis was induced in
Wistar rats by
intraperitoneal injection of
carbon tetrachloride (CCl4) three times weekly for 8 weeks. Then CCl4 was discontinued and
thalidomide (100 mg/kg) or its vehicle was administered daily by gavage for 6 weeks.
Serum hyaluronic acid,
laminin,
procollagen type III, and
collagen type IV were examined by using a
radioimmunoassay.
Matrix metalloproteinase-13 (
MMP-13),
tissue inhibitor of metalloproteinase-1 (
TIMP-1), and alpha-
smooth muscle actin (alpha-SMA)
protein in the
liver,
transforming growth factor beta1 (
TGF-beta1)
protein in
cytoplasm by using
immunohistochemistry and
Western blot analysis, and
MMP-13,
TIMP-1, and
TGF-beta1 mRNA levels in the
liver were studied using
reverse transcriptase polymerase chain reaction.
RESULTS:
Liver histopathology was significantly better in
rats given
thalidomide than in the untreated model group. The levels of
TIMP-1 and
TGF-beta1 mRNA and
protein expressions were decreased significantly and
MMP-13
mRNA and
protein in the
liver were significantly elevated in the
thalidomide-treated group.
CONCLUSION:
Thalidomide may exert its effects on the
regulation of
MMP-13 and
TIMP-1 via inhibition of the
TGF-beta1 signaling pathway, which enhances the degradation of
extracellular matrix and accelerates the regression of
hepatic cirrhosis in
rats.