NAKAMO Atsushi Tokai University, Internal Medicine3 Instractor, 医学部, 助手 (20246094)
KAGAWA Tatehiro Tokai University, Internal Medicine3 Assistant Professor, 医学部, 講師 (30245469)
WATANABE Norihito Tokai University, Internal Medicine3 Associate Professor, 医学部, 助教授 (90167156)
MATSUZAKI Syohei Tokai University, Internal Medicine3 Professor, 医学部, 教授 (40110902)
|Budget Amount *help
¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1997 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1996 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fibrosis of the liver is thought to be regulated by the balance between fibrogenesis and fibrolysis. To determine the role of matrix metalloproteinase (MMPs) as degradation enzymes of extracellular matrix and tissue inhibitor of metalloproteinases (TIMPs) as inhibitors of MMPs on hepatic fibrogenesis and on fibrolysis, we planned to investigate the altelations of immunohistochemical ditribution and serum levesl of type IV collagen (IV-C), MMP2, MMP3 and TIMP2 in patients with chronic hepatitis and cirrhosis.
Methods ; Liver specimens and serum samples were taken from patients with chronic persistent (CPH), active hepatitis (CAH) and cirrhosis (LC). Immunohistochemistry were done in both light and electron microscopically, using mouse anti-human IV-C,MMP2, MMP3 and TIMP2 monoclonal antibodis. Serum levels of IV-C,MMP2, MMP3 and TIMP2 were also measured using same antibodies by sandwich EIA method.
Results ; IV-C was partially appeared around widened portal area in CPH,then deposited around the proliferated bile ductules, microvessels and sinusoids near portal area in CAH.In LC,IV-C was strongly positive in fibrous septum and basement membrane in hepatic sinusoids. MMP2,3 and TIMP2 were demonstrated in pharenchymal cells (Ito cells, fibroblasts and Kupffer cells) in portal area, and in sinusoidal endithelial cells. The number of positively reacted cells with MMP2,3 and TIMP2 were tended to be increased in portal area and fibrous septum as parallel with progress of hepatic fibrosis. Serum levels of IV-C and MMP2,3 were significantly increased in LC compared to CPH and CAH.There was the positive correlation between IV-C and MMP2, associated with the progress of hepatic fibrosis (r=0.73).
Conclusions ; Both TIMPs and MMPs seems to be activated in parallel with liver fibrosis, thus increase of serum MMP2,3 levels might be associated with increased MMP2,3 positive cells in liver tissue.