Hepatocyte production of modulators of extracellular liver matrix in normal and cirrhotic rat liver.
In the present study, we found collagenolytic and gelatinolytic activity in the supernatants of hepatocyte cultures from rats with experimental CCl(4)-induced liver cirrhosis, in levels significantly higher than in comparable supernatants of hepatocyte cultures from normal rats. In addition, we clearly detected the messenger ribonucleic acids (mRNA) of four matrix metalloproteinases (MMP-2, MMP-3, MMP-10, and MMP-13) and of two tissue inhibitors of matrix metalloproteinases (TIMP-1 and TIMP-2) in hepatocytes from both normal and cirrhotic rats by RT-PCR and by in situ hybridization. Finally, we demonstrated MMP-2, MMP-3, and MMP-13 and TIMP-1 and TIMP-2 proteins in the same hepatocyte preparations by immunostaining. We conclude that rat hepatocytes produce the major enzymes and inhibitors involved in liver ECM modulation and therefore suggests that they might participate actively in the pathophysiology of liver cirrhosis in rats.
Garcíade León
María del Carmen
Mdel C
Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, y Hospital General, de México, D.F. 06720, México.
Montfort
Irmgard
I
Tello Montes
Eusebio
E
López Vancell
Rosario
R
Olivos García
Alfonso
A
González Canto
Augusto
A
Nequiz-Avendaño
Mario
M
Pérez-Tamayo
Ruy
R
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology / Q000473:pathology; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008297:Male; D045726:Metalloproteases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D045726:Metalloproteases