H. Yasuda et al., ANTIFIBROGENIC EFFECT OF A DELETION VARIANT OF HEPATOCYTE GROWTH-FACTOR ON LIVER FIBROSIS IN RATS, Hepatology, 24(3), 1996, pp. 636-642
Hepatic fibrosis, which may lead to cirrhosis, is associated with most
chronic liver diseases, Current therapies for hepatic fibrosis are, h
owever, generally ineffective, In this report we assessed the efficacy
of the treatment of hepatic fibrosis with a naturally occurring delet
ion variant of hepatocyte growth factor (dHGF). The administration of
dHGF increased liver weight and suppressed the increase of hepatic col
lagen content in rats treated with dimethylnitrosamine (DMN) to induce
hepatic fibrosis, Furthermore, dHGF exerted its mitogenic and antifib
rogenic activities even after the liver fibrosis had been established
with DMN, Northern blot analysis showed that dHGF suppressed the incre
ase of messenger RNA (mRNA) levels of procollagen alpha 2(I), alpha 1(
III), alpha 1(IV), transforming growth factor beta(1) (TGF-beta(1)), d
esmin (a marker of hepatic lipocytes), and alpha-smooth muscle (sm)act
in (a marker of activated hepatic lipocytes), In addition to suppressi
ng the elevated TGF-beta(1) mRNA level in hepatic fibrosis, dHGF had a
potent ability to decrease TGF-beta(1) mRNA level even in a normal li
ver, Immunohistochemical analysis revealed that desmin-positive cells
and alpha-sm-actin-positive cells were increased in the hepatic fibros
is, whereas neither cells were seen in livers of DMN-treated rats give
n dHGF, We conclude that dHGF prevents and improves the DMN-induced he
patic fibrosis in rats by reducing mRNA levels of procollagens and TGF
-beta(1), by inhibiting an activation of hepatic lipocytes, and by sti
mulating liver regeneration. dHGF may be useful for and applicable to
the treatment of fibrosis in chronic liver diseases.