K. Uetsuka et al., IMMUNOHISTOCHEMICAL STUDY ON GALACTOSAMINE-INDUCED SUBACUTE HEPATITISIN RATS OF JCL - WISTAR-TGN (ARGHGEN) 1NTS STRAIN (MINI RATS), Experimental animals, 46(3), 1997, pp. 203-209
Immunohistochemical study was carried out on D-galactosamine hydrochlo
ride (GalN)-induced subacute hepatitis in rats of JCL:Wistar-TGN (ARGH
GEN) 1Nts strain (Mini rats), in which the expression of growth hormon
e gene is suppressed by the presence of an antisense transgene. Mini r
ats were given 1000 mg/kg of GalN once a week for 4 consecutive weeks
and killed at 1, 2, 3 and 4 weeks after the first administration. At I
week after the first administration, proliferation of small epithelia
l cells positive for both crfetoprotein and cytokeratin 7, i.e. so-cal
led oval cells, was observed in the whole area of each hepatic lobule,
and prominent deposition of fibronectin, laminin and type IV collagen
was detected around these oval cells. Together with these extracellul
ar matrix components, many activated Ito cells positive for both desmi
n and alpha-smooth muscle actin were obsereved With time, most of the
oval cells formed duct-like structures and lost their positive stainab
ility for alpha-fetoprotein, and many Ito cells became inactive. Depos
ition of fibronectin decreased rapidly from 2 weeks after the first ad
ministration. At 4 weeks after the first administration, deposition of
laminin was detected only around the duct-like structures, where that
of type IV collagen was also still prominent. These results suggest t
hat a large population of oval cells differentiated into bile duct epi
thelial cells and that Ito cells and extracellular matrix components m
ight play a role in this process.